Aiming at the problem that antibiotic pollution in soil is becoming more and more serions, in order to promote the improvement of antibiotic monitoring technical system and related standards, a method of QuEChERS combined with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established. The soil samples were extracted with 10 mL 3% ammoniated acetonitrile (V/V), purified with 02 g PSA and 02 g anhydrous MgSO4, the mobile phase was methanol-water (1∶1, V/V), the UPLC column used in the experiment was ZORBAX SB-Aq (21 mm×150 mm,35 μm), the ion source was electrospray ion source(ESI) with positive/negative ion scanning, and the detection method was multiple reaction monitoring(MRM).The results indicates that the linear relationships of the four analytes are good in the range of 01~200 ng/mL, with a correlation coefficients(r) higher than 0999, the limits of detection (LOD) and the limits of quantitation(LOQ) are 001~006 μg/kg and 005~019 μg/kg, respectively; the average recoveries are 8723%~10857% at three spiked levels(04, 80,400 μg/kg), the relative standard deviations (RSDs, n=5) are 036%~655%.The method is accurate, simple, efficient and sensitive, which is suitable for the simultaneous determination of chloramphenicol, sulfoxamycin, flufenicol and its metabolite florfenicol amine in soil， and provides data basis for setting relevant standards and regulations.