Objective: A confirmatory method has been established for determination of chloramphenicol residue in aquatic products such as fish and shrimp muscles by UPLC-MS/MS.Samples were extracted with ethyl acetate.Methods:The extracts were separated on an Acquity UPLC BEH C18 column(55 mm×2.1 mm×1.7 μm(i.d)) by mobile phase of acetonitrile and water at ration of 4:6.The detection was carried on a mass spectrometer coupled with EST and MRM negative mode.Calibration was by the internal standard method.The limit of detection was 0.01 μg/kg(S/N≥3),and limit of quantitation was 0.05 μg/kg.Results:The recoveries of the method were from 83.0% to 95.0%,the RSD between 2.50% and 6.2%.Conclusion:This approach is a easy,fast,sensitive and accurate method with little cross contamination.