Long-term use of niclosamide (NCL) in schistosomiasis control areas may have a certain impact on the regional ecological environment. The purpose of this study is to investigate the NCL residue and its possible degradation intermediates in the Wucheng water in the Poyang Lake Basin of China, and assess its ecological risks. Water samples were collected at twelve sites every month from July 2017 to June 2018, the collected samples were qualitatively and quantitatively analyzed by HPLC and HPLC/MS techniques, and regional ecotoxicological risks were estimated by calculating risk quotients (RQ). The results indicated that due to the use of NCL, the regional water environment contained NCL, 2-chloro-4-nitroaniline, 5-chlorosalicylic acid and 2,5-dihydroxybenzoic acid, etc, and their concentrations were 0.000~0.028 μg/L, 0.000~0.015 μg/L, 0.000~0.019 μg/L, below detectable limit, respectively. The mixed risk quotient (MRQ) for sensitive aquatic organisms algae, invertebrates and fish was 0.000~0.707, 0.000~0.864, 0.000~0.935, respectively. These findings demonstrated that the mixture of NCL residues and their intermediates has a moderate risk to sensitive aquatic organisms such as algae, invertebrates and fish in Wucheng waters. In order to protect the regional water environment, it is necessary to strengthen the supervision and management work after the application of NCL drugs.