Depression is the second leading-cause of disability in China. Although studies have shown that more than 80% of patients with advanced schistosomiasis (AS) suffer from anxiety and depression, these study groups are all hospitalized patients with AS and do not represent the extent of the disease in the whole group. To our knowledge, there are no studies assessing the severity of depression in patients with other forms of schistosomiasis japonicum. Therefore, it is necessary to evaluate the occurrence and potential risk factors of depression in the schistosomiasis endemic population. This cross-sectional study was conducted in Jiangxi Province, where schistosomiasis is relatively common in China, as the investigation site. The Patient Health Questionnaire-9 (PHQ-9) scale was selected to assess the depressive symptoms in the study population. At the same time, basic personal information of the research subjects and relevant socio-economics and schistosomiasis endemic area indicators were collected. The survey results show that AS has the highest incidence of depression (34.35%), while non-advanced schistosomiasis (N-AS) and control group (CG) have 22.35% and 22.24% respectively; the incidence of depression in AS is significantly higher than in N-AS and CG, while there is no statistical significance in the comparison between N-AS and CG; the incidence of mild depressive symptoms accounts for 61.08%-75.54% of the total incidence of depression in different groups; multivariate analysis shows that the occurrence of moderate/severe depressive symptoms in the AS group was significantly related to above 60 years old, male, the combination of other serious diseases, personal financial difficulties, and marshland and lake endemic areas. In the N-AS group, the occurrence of moderate/severe depressive symptoms was significantly related to the combination of other serious diseases, personal financial difficulties, significant correlation between marshland and lake endemic areas and the level of control of schistosomiasis epidemics. In conclusion, depression is still relatively common among patients with schistosomiasis patients, especially those with AS. It is recommended that the government and relevant departments consider mental health care when developing prevention and control work in schistosomiasis-endemic areas, in order to effectively protect the physical and mental health of schistosomiasis patients and residents in endemic areas.