Abstract: The residue behaviors of thiamethoxam in Benincasa hispida Cogn. var. chieh-qua How (chieh-qua) were investigated. The residue field trials of thiamethoxam were designed and conducted in Guangdong and Shanghai in 2015. An effective method was developed for the determination of the thiamethoxam and clothianidin. The chieh-qua samples were extracted by acetonitrile, purified with aminopropyl solid phase extraction and detected using HPLC-MS/MS (high performance liquid chromatography-tandem mass spectrometry). The dissipation and terminal residues of thiamethoxam and clothianidin in chieh-qua samples in Guangdong and Shanghai were determined based on the above analytical method. The results indicated that the half-lives of thiamethoxam in chieh-qua was 4.98-5.84 d. The chieh-qua was sprayed 2 to 3 times with 7-10 days spray interval using 25% WG at the dosage 75 and 112.5 g/hm² during the young fruit period. The samples were collected 3 to 7 days after the last spray. The terminal residues of thiamethoxam and clothianidin were 0.010-0.422 mg/kg and <0.010-0.020 mg/kg, respectively, which were determined by the conditions above. The risk quotients (RQ) was 0.044, which revealed its low risk. According to the results, it is suggested that the MRL of thiamethoxam in chieh-qua in China should be set as 1 mg/kg.