Abstract: 113 Organophosphorus, organochloride and pyrethroid pesticide residues in tobacco samples were extracted and purified by using QuEChERS method, separated by the DB-17 capillary column. Interference of complex matrix and pesticide components of overlapping peaks crosstalk could be effectively reduced by optimizing triple quadrupole mass spectrometer(GC-MS-MS) parameters, so as to qualitative and quantitative by retention time window and selective reaction monitoring(SRM) with peak area. The method was easy for pre-treatment, efficient and solvent saving, which could determine 124 pesticide components with one injection in 50 min, precisely and sensitivity. The method was certificated by more than 200 tobacco samples and the result was promising.