Objective To understand the prevalence of clonorchiasis among people in high endemic areas in Guangdong Province from 2016 to 2020, and to provide a basis for the formulation of prevention and control strategies. Methods For surveillance on clonorchiasis from 2016 to 2020, in Χinhui district of Jiangmen City, Guangdong Province, five regions were designated according to the geographic position in the east, west, south, north and middle part, from each of them, one township (town) was randomly selected as regular surveilence site in Χinhui District of Jiangmen City, Guangdong Province including Da’ao, Sanjiang, Shadui, Siqian, and Yamen. Every year, over 200 permanent residents aged 3 or above were cluster selected from an administrative village of each selected town. Fecal samples were collected from the participants and examined for Clonorchis sinensis eggs using the Kato-Katz thick smear method (two slide readings per sample). Pearson’s chi-squared test was used to compare the rates between groups. Results From 2016 to 2020, a total of 5116 fecal samples were collected and examined from five surveillance sites in Xinhui District, with a overall infection rate of 14.6% (749/5 116). The annual infection rates of C. sinensis from 2016 to 2020 were 23.1% (237/1 025), 15.5% (156/1 005), 13.1% (134/1 021), 13.8% (142/1 031), and 7.7% (80/1 034), respectively, showing a downward trend. The difference in infection rate between different years was statistically significant (χ² = 101.56,P < 0.01). The infection rates in residents at the five regular surveillance sites were 38.7% (404/1 045) in Da’ao, 13.9% (142/1 025) in Siqian, 10.5% (105/1 003) in Sanjiang, 6.0% (61/1 017) in Shadui and 3.6% (37/1 026) in Yamen. The infection rate in different regions was statistically significant(χ² = 657.67,P < 0.01). The average age of the infected was 43.1 years old. The lowest infection rate of 5.6% (79/1 415) was seen in the age group of < 18 years, while the highest infection rate of 20.6% (97/47) was seen in the age 61-70 group. The infection rate in different age groups was statistically significant (χ² = 137.0, P < 0.01). Among all occupations, the highest infection rate of 24.7% (36/146) was seen in public servants. There was a statistically significant difference in the infection rate among different occupations (χ² = 156.44, P < 0.01). The infection rate among illiterate and semi-illiterate people was 16.8% (17/101). There was no significant difference in the infection rate among people with different education levels(χ² = 9.33, P > 0.05). The average infection rates in 2016—2020 were 16.5% (412/2 492) and 12.8% (337/2 624) for males and females, respectively. The infection rate in males was significantly higher than that for females (χ² = 13.93, P < 0.01). Of all the infected individuals, 97.2% (728/749) were infection, 2.8% (21/749) moderately infection, and no severe infections. Conclusion The surveillance conducted from 2016 to 2020 indicated tha C. sinensis infection in residents in the high endemic areas of the Guangdong Province remained considerably high but showed an overall decreasing trend, with mainly having mild infection. Based on the results, future surveillance needs to stress on the males aged over 18 years.