Abstract: In order to fill the gap in the field, a gas chromatography-tandem mass spectrometry multi-reaction monitoring mode (MRM) was established for the determination of pydiflumetofen residue in tobacco, and the digestion resolution dynamics of pydiflumetofen in tobacco were analyzed through field experiments. The results show that the method has good linearity in the mass concentration range of 0.001~0.5 mg/L, and the correlation coefficient R²=0.999 5; RSD was 4.57% when repeated determination of the same test sample, and the limit of quantification was 0.012 mg/kg. At 0.012, 0.12 and 0.5 mg/kg supplemental levels, the average recovery rate ranged from 92.6% to 101.7%, and RSD ranged from 2.6% to 4.5%. The digestion trend of pydiflumetofen in tobacco in Sichuan and Shandong was in line with the first-order kinetic equation. The digestion rate of pydiflumetofen in tobacco was more than 50% and 90% at sampling interval of 5 d and 35 d, the theoretical half-life of pydiflumetofen in tobacco was between 5.73 d and 9.12 d. MRL is not established in China or by CORESTA for detection method standards for pydiflumetofen in tobacco, and the research results can provide data and method reference for the formulation of limit standards and detection standards.