Abstract: An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for determining the organochlorine herbicide residues, including dicamba, 2,4-D, and 2,4,5-T,in tobacco-growing soil was developed. Stable isotopic-labels were used as internal standards, including dicamba-d₃,2,4-D-d₃, and 2, 4,5-T-d₂, for the quantitative analysis of each compound. Soil samples were extracted with acetonitrile, purified by N-propylethane-1,2-diamine (primary secondary amine, PSA), filtered by 0.45μ m microporous membrane and subsequently analyzed by LC-MS/MS. It took only 4 minutes to complete the analysis. The proposed method displayed good linearity in the range from 1 to 100 ng/mL with R² higher than 0.99, the limit of detections of dicamba,2,4-D, and 2,4,5-T were 0.025, 0.002 and 0.003 ng/mL, respectively. At the standards' addition levels of 20, 100 and 400 ng/g in soil extract, the average recoveries of organochlorine herbicides ranged from 84.8% to 104.1% with the RSD of 2.1% to 10.4%. The developed method is accurate, reliable, sensitive and suitable for the quantitative analysis of dicamba, 2,4-D and 2,4,5-T residues in tobacco-growing soil.