Abstract: A simultaneous method for the determination of 54 drugs residues (sulfonamides, nitroimidazoles, quinolones, macrolide antibiotics, lincosamides and praziquantel) in pork was developed and validated by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) following solid phase extraction (SPE). The extracts were dissolved and distilled with acetonitrile. After that the supernatant solution was extracted with n-hexane to remove the fat, and then cleaned up with SPE C₁₈ cartridges. The quantitative detection was performed on LC-MS/MS by multiple reaction monitoring (MRM) mode under positive electrospray ionization (ESI⁺). The one precursor/two product ion transitions were used for each compound. Isotopes dilution internal standard method was used to determine the residue contents in pork. The limits of quantification (LOQs) are 1.0 μg/kg (sulfonamides and nitroimidazoles), 2.0 μg/kg (quinolones and lincosamides), 3.0 μg/kg (macrolide antibiotics) and 0.3 μg/kg (praziquantel), respectively. Validation parameters are determined as follow correlation coefficients， which are more than 0.991, and the recovery for each analyte ranges of 20.9%—121% with relative standard deviations (RSDs) between 2.0% and 19.8%.