Abstract: In order to rapidly detect veterinary drug residued in fish, a UPLC-MS/MS detection method for simultaneous detection of fluorobenzicol (FF), fluorobenzicolamine (FFA), oxytetracycin hydrochloride (OTC) and sulfamethoxazole (SMZ) in fish fish samples was established through sample extraction and detection condition optimization, and a methodology evaluation was conducted according to the European Union 2002/657/EC. The results show that all the analysis and testing conditions and methodological evaluation indicators of this method meet the requirements of EU 2002/657/EC.This method has good linearity for 4 veterinary drugs . The detection limit is 0.25~5 μg/kg and the limit of quantification is 0.5~10 μg/kg. The determination limit is 102.8~129 μg/kg. Detection capacity is 108.2~170 μg/kg; recovery rate is 89.7%~106.5%; CV ≤ 10.8% during the day. This method was used to detect 88 fish samples collected in Xindu District of Chengdu. The data showed that the main antibiotic residue in the fish collected in this area was florfenicol, and the residual amounts were lower than the maximum residue limit value specified by the national standard.