Abstract: A method was established for the simultaneous determination of multiple receptor agonist drug residues in pork by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After enzymatic hydrolysis, the samples were extracted by acidic acetonitrile, and cleaned up by pass-type PRIME HLB, then detected by UPLC-MS/MS in the positive mode and multiple reaction monitoring (MRM) mode, and quantified by the external standard method. Results showed that, good linear relationship were obtained for the 11 multiple receptor agonist drugs in the range of 0.1~100 μg/L, with coefficients of determination between 0.9992 and 0.9999. The limits of detection (LOD) for the method were 0.5 μg/kg, the average recoveries of all compouds were between 81.3% and 117.6%, with the relative standard deviations varying from 0.7% to 6.5%. The method was simple and would be suitable for simultaneous determination of multiple receptor agonist drug residues in pork.