Abstract: In order to reduce matrix interference and improve detection sensitivity and stability, a method for determination of hymexazol residues in tobacco was established using QuEChERS as sample pretreatment method and liquid chromatography tandem mass spectrometer as detection instrument. The samples were extracted by acetone after moistened with water, then bytreated with salting-out reagent to remove water and purified by graphitized carbon black (GCB). After separated by Agilent ZORBAX 300SB- C8 column (2.1 mm×100 mm, 1.8 μm) with methanol-water as the mobile phase，the extracts were detected by an electrospray ionization (ESI) tandem mass spectrometry in the multiplereaction-monitoring (MRM) mode. The results showed that good linearity was obtained in the range of 0.0025-0.0500 mg/L, the linear correlation coefficient (r²) was 0.9996, the quantitative detection limit was 1.06 μg/L, the recovery ratio was between 90.8%-92.0%, and the relative stantdard deviation was 5.1%. With simple operation and high detection accuracy, this method is suitable for hymexazol determination in tobacco, which meets CORESTA's requirements for tobacco pesticide residue detection.