Abstract: In order to analyze two common chlorinated phenoxy acid residues in tobacco, an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantifying 2, 4-D and 2, 4, 5-T was proposed. The analytes were extracted from tobacco samples by a hydrochloric acid solution and CH₂Cl₂. The extract was analyzed qualitatively and quantitatively by a tandem mass spectrometer in multiple reaction monitoring (MRM) mode after being separated on C₁₈ column. The results showed that:1) A good linear relation was obtained in the range of standard working solution with r > 0.999. The limits of detection (LODs) and quantification (LOQs) were 0.004 5-0.007 6 and 0.013 8-0.023 6 mg/kg, respectively. The added standard recoveries of blank samples ranged from 79.5% to 94.6% with the relative standard deviations less than 6.0%. 2) The method was applied to 30 different types of tobacco samples, the results agreed well with those obtained by the tobacco industry standard method based on GC-MS. The proposed method is rapid and sensitive, no derivatization required, and consumes less organic reagents. It is suitable for the analysis of 2, 4-D and 2, 4, 5-T in flue-cured tobacco, burley tobacco and oriental tobacco.