Objective To understand and analyze the epidemic status and development trends of soil-transmitted nematodiasis in Guangxi Zhuang Autonomous Region (Guangxi), to provide scientific basis for formulating the disease control strategy, and evaluating the control effect. Methods In 2016—2020, Guangxi was assigned to high-, medium- and low-GDP regions, from which 39 counties (cities, districts) were selected as surveillance sites. Each county under surveillance was divided into 5 regions according to geographic location, i.e., east, west, south, north, and central. From each region, one townships was randomly selected, and an administrative village was selected from the township for the surveillance. In the sampled village, no less than 200 permanent residents aged > 3 years were cluster sampled for examination. Fecal samples were collected from the villagers, and soil-transmitted nematode eggs were detected with the modified Kato-Katz thick smear method. The eggs of Enterobius vermicularis were examined in children aged 3-9 years with the adhesive tape method. Chi-square test and Chi-square trend test were used to analyze and compare the infection status of soil-transmitted nematodes in different areas, gender, age groups, nationalities, education levels and occupations. Results In the 39 surveillance sites, the production modes was mainly agriculture, and the drinking water was mostly tap water and well water. From 2016 to 2020, the coverage rates of sanitary toilets was 77.39% (36 403/47 040), 94.19% (47 120/50 026), 94.47% (55 499/58 750), 86.72% (68 913/79 467), and 94.99% (56 188/59 154), respectively, which differed significantly (χ² = 12 813.53, P < 0.05). A total of 66 355 people were examined, and the infection rates of soil-transmitted nematodes were 4.20% (533/12 699), 2.98% (312/10 458), 2.21% (276/12 485), 1.75% (285/16 329) and 1.54% (222/14 384) in 2016—2020, respectively, showing significant difference between years (χ² = 260.67, P < 0.05), and a decreasing trend year by year (χ² = 316.05, P < 0.05). The rates in the high-, medium- and low-GDP areas were 1.11% (244/22 049), 2.65% (722/27 273) and 3.89% (662/17 033) respectively, and differed significantly between the areas (χ² = 317.57, P < 0.05). The hookworm infection rate in females was 2.68% (900/33 548), which was higher than that in males (1.40%, 458/32 807) (χ² = 136.98, P < 0.05). The Trichuris trichura infection rate in males and females were 0.29% (95/32 807) and 0.32% (108/33 548), respectively; the Ascaris lumbricoides infection rates in males and females were 0.11% (37/32 807) and 0.13% (43/33 548), respectively; and the E. vermicularis infection rates in boys and girls were 11.69% (274/2 343) and 12.17% (257/2 112), respectively. There was no significant differences in the infection rate between genders (χ² = 0.569, 0.326, 0.24; P > 0.05). Among the different age groups, the infection rate of hookworm was highest in the group aged > 80 years, at 4.93% (69/1 399); the rate of A. lumbricoides was highest in the group aged 3-9 years, at 0.28% (31/11 183); and the rate of T. trichura was highest in the group aged 70-79 years, at 0.62% (31/4 961). The infection rate of hookworm was the highest in the Zhuang minority population at 2.77% (870/31 352); and the rates of A. lumbricoides and T. trichura were highest in other minorities, both at 0.60% (18/2 976). The infection rates of hookworm and T. trichura were highest in the illiterate group, at 5.36% (195/3 635) and 0.61% (22/3 635) respectively. The A. lumbricoides infection rate was highest in preschool children, at 0.35% (20/5 674). The infection rate of hookworm was highest in farmers, at 2.80% (1 285/45 943); that for A. lumbricoides in live-scattered children, at 0.71%(10/1 399); and that of T. trichura in institutional personnel, at 0.45% (5/1 105). The infection rate of E. vermicularis in children aged 3-9 years was 8.45% (24/284), 17.99% (86/478), 15.66% (155/990), 11.48% (182/1 586) and 7.52% (84/1 117) in 2016—2020, respectively, which differed significantly (χ² = 54.10, P < 0.05), and showed an increasing trend and then a decreasing trend with time (χ² = 21.07, P < 0.05). Conclusion The infection rate of soil-transmitted nematodes in Guangxi decreased year by year, and displayed low prevalence. However, the E. vermicularis infection rate in children maintained at a considerable high level. Therefore, it is imperative to strengthen comprehensive prevention and control measures in children.