Abstract: Objective: A method of determination of chloramphenicol, sulfamerazine, sulfadimidine, sulfathiazole, trimethoprim, and sulfadiazine in pork by ultra-high liquid chromatography-tandem mass spectromrtry ( UPLC-MS/MS) was developed.Method: Samples were extracted with ethyl acetate precipitated protein at the same time and dried under nitrogen. The residue was dissolved with 10% acetonitrile solution and defatted by cyclohexane. Samples were detected by UPLC-MS/MS and isolated with UPLC BEH C₁8.The liquid phase was acetonitrile and water. The electrospray ionization ( ESI) mass spectrometry had run in multiple reaction monitoring mode ( MRM) .Result: At these experimental conditions, chloramphenicol had good liner relatively ( R²> 0.99) between 9.6 ~ 384 ng/kg. And sulfamerazine, sulfadimidine, sulfathiazole, trimethoprim and sulfadiazine had good liner relatively ( R²> 0.99) between 0.51²0.8 μg/kg.Limits of detection were 3.2 ng/kg for chloramphenicol, 0.158⁰.173 μg/kg for 5 kinds of sulfonamides ( sulfamerazine, sulfadimidine, sulfathiazole, trimethoprim, sulfadiazine) . Limits of quantitation were 9.6 ng/kg for chloramphenicol, 0.475⁰.52 μg/kg for 5 kinds of sulfonamides ( sulfamerazine, sulfadimidine, sulfathiazole, trimethoprim and sulfadiazine) . Average recoveries were 70.84% ~ 103.99% with relative standard deviations of1.98% ⁸.01%. Conclusion: This method could detect the chloramphenicol, sulfamerazine, sulfadimidine, sulfathiazole, trimethoprim, and sulfadiazine residue in pork with a better precision, higher accuracy and better specificity.