Objective To investigate the epidemiological characteristics of, and knowledge, attitude, and practice towards Clonorchis sinensis infections in humans in Binyang County, Guangxi in 2022, for providing insights into formulation of targeted control measures. Methods Binyang County in Guangxi was geographically divided into five regions (eastern, western, southern, northern, and central) in 2022, and one township was sampled from each geographical region, followed by one administrative village (community) sampled from each township. Two hundred residents at ages of over 3 years were sampled from each administrative village (community) using a cluster sampling method, and participants’ stool specimens were sampled for detection of C. sinensis eggs using a modified Kato-Katz thick smear method (two smears from one stool sample). One questionnaire survey was performed in each household, and 40 residents were sampled from each village for individual questionnaire surveys on knowledge, attitude, and practice towards clonorchiasis control. The differences in the awareness of clonorchiasis control knowledge, practice towards consumption of raw freshwater fish, and attitude to consume raw freshwater fish were compared among different participants with Chi-square test or Fisher’s exact test. In addition, univariate and multivariate logistic regression models were employed to identify factors affecting the prevalence of C. sinensis infections in humans, practice of consuming raw freshwater fish, and attitude towards consumption of raw freshwater fish in future among participants. Results A total of 1 007 residents received stool examinations, and 372 household questionnaire surveys and 202 individual questionnaire surveys were completed, including 175 individuals completing both stool examinations and questionnaire surveys. The overall prevalence of C. sinensis infections was 15.49% [95% confidential interval (CI): (13.25%, 17.73%)] among participants, with the highest prevalence in Silong Township [22.00%; 95% CI: (15.84%, 27.38%)] (P < 0.05), and the prevalence was higher in males [26.32%; 95% CI: (22.27%, 30.06%)] than females [5.07%; 95% CI: (3.16%, 6.97%)] (P < 0.05). The prevalence of C. sinensis infections in humans raised and then decreased following the increase of ages, with a peak at ages of 45 to 59 years [24.31%; 95% CI: (19.01%, 29.61%)] (P < 0.05), and the highest prevalence was found among participants with an educational level of junior high school [23.77%; 95% CI: (19.89%, 27.64%)] (P < 0.05). Among the 372 households surveyed, the proportions of households preparing raw freshwater fish less than once, once to 10 times, 11 to 50 times and more than 50 times annually were 4.03% (15/372), 21.77% (81/372), 15.06% (56/372) and 8.60% (32/372), respectively. Notably, Binzhou Township recorded the highest proportion of households preparing raw freshwater fish once to 10 times annually (83.64%, 46/55), and Xinxu Township recorded the highest proportion of households preparing raw freshwater fish 11 to 50 times annually (50.47%, 54/107) and more than 50 times annually (29.91%, 32/107), respectively (P < 0.05). The highest proportion of households that had purchased raw freshwater fish from outside was found in Silong Township (35.09%, 20/57) (P < 0.05), and the highest proportion of households that had presented raw freshwater fish to their neighbors was seen in Binzhou Township (51.81%, 43/55) (P < 0.05), while both the highest proportion of households that had received raw freshwater fish from neighbors (99.07%, 106/107) and did not separate raw and cooked chopping boards in daily life (98.08%, 102/104) was found in Xinxu Township (P < 0.05). The awareness of hearing of clonorchiasis, knowing the transmission route of clonorchiasis and knowing the harm of clonorchiasis was 54.46% (110/202), 50.00% (101/202) and 38.12% (77/202) among all participants, with 63.00% (63/100), 59.00% (59/100), and 46.00% (46/100) in males and 46.08% (47/102), 41.18% (42/102), and 30.39% (31/102) in females, respectively (P < 0.05), and the awareness was higher in Gula Township (92.50%, 37/40; 92.50%, 37/40; 90.00%, 36/40), among the elderly at ages of 60 years and older (71.43%, 45/63; 63.49%, 40/63; 50.79%, 32/63), Han ethnic group (58.29%, 102/175; 54.29%, 95/175; 41.14%, 72/175), and participants with an educational level of senior high school and above (87.50%, 14/16; 81.25%, 13/16; 62.50%, 10/16) (P < 0.05). There were 26.73% (54/202) of respondents reporting ingestion of raw freshwater fish, with a higher percentage in Silong Township (45.00%, 18/40) (P < 0.05). The percentage of consuming raw freshwater fish was higher in males (45.00%, 45/100) than females (8.82%, 9/102) (P < 0.05), and the highest proportion of consuming raw freshwater fish was seen among participants at ages of 30 to 44 years (42.31%, 11/26) (P < 0.05). There were 80.69% (163/202) of respondents that were willing to stop consuming raw freshwater fish in future, with a higher proportion in females (97.06%, 99/102) than males (64.00%, 64/100) (P < 0.05). Univariate logistic regression analysis showed that C. sinensis infection was associated with gender, age, awareness of clonorchiasis, frequency of preparing and consuming raw freshwater fish and way of acquiring raw freshwater fish (P < 0.05), and the practice of consuming raw freshwater fish was associated with gender, awareness of clonorchiasis, understanding routes of C. sinensis infection, having experiences of preparing raw freshwater fish, having experiences of purchasing raw freshwater fish from outside, and having experiences of presenting or receiving raw freshwater fish (P < 0.05), while factors affecting the attitude towards consumption of raw freshwater fish in future included gender, age, positive fecal test, frequency of consuming raw freshwater fish, and having experiences of receiving raw freshwater fish from neighbors (P < 0.05). Multivariate logistic regression analysis revealed that the prevalence of C. sinensis infections was 30.01 [95% CI: (7.56, 152.04)] times among respondents consuming raw freshwater fish once to 5 times annually and 81.40 [95% CI: (7.78, 287.37)] times than among those consuming raw freshwater fish more than 5 times annually relative to individuals without ingestion of raw freshwater fish, and the prevalence was 15.18 [95% CI: (2.15, 123.25)] times higher among respondents that had received raw freshwater fish from their neighbors than among those who had not. The proportion of consuming raw freshwater fish was 17.58 [95% CI: (6.21, 61.88)] times in males than females, and the proportion of consuming raw freshwater fish was 15.75 [95% CI: (1.40, 185.99)] times among respondents that knew clonorchiasis than among those who did not, while the percentages of continuing to consume raw freshwater fish were 3.66 [95% CI: (1.85, 4.32)] times among respondents with consumption of raw freshwater fish once to five times annually and 3.55 [95% CI: (1.17, 3.03)] times among those with consumption of raw freshwater fish more than five times annually than among individuals without consumption of raw freshwater fish. Conclusion The prevalence of C. sinensis infection is high in Binyang County, Guangxi, notably among adult males, and the special dietary habit of consuming raw freshwater fish is the major cause of C. sinensis infections among human. Intensified health education and changes of the behavior of consuming raw freshwater fish are required to achieve sustainable clonorchiasis control.