A high throughput quanti cation multi-residues method for the simultaneous detection of 39 pesticides and veterinary drugs in aquaculture products were developed by using Ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) with modi ed QuEChERS (quick easy cheap effective rugged safe). In order to balance recovery and detection e ciency, several parameters were optimized, including extracting, clari cation, and puri cation. Chromatographic conditions were optimized to given run time of 13 min. Six representative matrices (muscle tissues of yellow croaker, pomfret, shrimp, white shell, ower shell, razor clam) show applicability with all target analytes showed recoveries (60.3%~119.0%) and acceptable precision (4.3%~20.8%). Furthermore, detection limits (LODs) and limits of quanti cation (LOQs) in the range of 1.0 ~ 5.0 µg/kg and 3.0 ~ 10.0 µg/kg, respectively, that providing a practical safety quanti cation method for internal risk controlling by aquaculture.