A method was developed for the simultaneous determination of 20 sulfonamides and 8 quinolones antibiotic residues in meat by QuEChERS and ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).Methods The analytes were extracted with 1% formic acid acetonitrile and cleaned up with dispersive-solid phase extraction. The target analytes were separated by Waters C₁₈ column with gradient elution. The analytes were detected by tandem quadrupole mass spectrometry after positive electrospray ionization by multiple reaction monitoring (MRM). External standard method was used to determine the results. Results The correlation coefficients of 28 antibiotics ranged from 0.997 5 to 0.999 6 in the linear range. The limits of detection were 0.17-0.91 μg/kg (S/N=3). The recoveries of sulfonamides and quinolones were 70.9% to 115.2% and 71.3%-112.3% respectively. The RSDs of sulfonamides and quinolones were 2.8%-15.9% and 2.5%-14.6%(n=6) .Conclusion The method was effective, rapid, sensitive, and suitable for the monitoring of multi-antibiotic residues in animal derived foods.