In order to provide more technical references on drugs multi-residue analysis in soil, A UPLC-MS/MS method combined with QuEChERS to simultaneously determine 47 drugs from 11 categories in soil was established. Separation effect of different columns and mobile phases on analystes was addressed. Extraction effect of EDTA-Mcllvaine buffer solution with different pH and purification effect of d-SPE dispersers on drugs was analyzed as well. 47 drugs have good linearity with r≥0.995. LODs of 47 compounds ranged from to 0.1μg·kg-1and 2.5μg·kg-1, LOQs were 0.5μg·kg-1～8μg·kg-1. Recoveries varied between 61.1% and 117.0%, RSDs was 1.9%～11.4%. This UPLC-MS/MS method is sensitive and suitable for accurate and high throughput analysis of multiclass drugs residues in soil, useful for analysis of occurrence characteristics of drugs residues in soil and risk assessment.