Abstract: A multi-residue analysis method was developed for the determination of 79 pesticides in Pinelliae Rhizoma processed products using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). This method was applied in the screening of 217 batches (including Pinelliae Rhizoma Praeparatum(PRP), Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine(PRZ) and Pinelliae Rhizoma Praeparatum cum Alumine(PRA)). The samples were extracted with acetonitrile and cleaned up by PSA. Then they were detected by UPLC-MS/MS with multiple reactions monitoring (MRM) mode. Detection results were analyzed by statistical software and the differences among processed products were compared. The results showed that all the pesticides had good linearity when the concentrations varied from 1 to 100 μg/L with the coefficient of determination (R²) higher than 0.99. More than 81.0% of the tested pesticides had recovery rates between 70% to 120% with the RSDs less than 15% (n = 6) under the three spiked levels (5 × limits of detection (LOD), 10 × LOD and 20 × LOD). The limits of quantitative (LOQs) of this method ranged from 0.0001 to 0.1 mg/kg. 27 pesticide residues were detected in 217 batches of samples. Statistical analysis showed that the detection results of carbendazim and carbofuran were significantly different between PRP and PRZ, PRP and PRA. This method was proven to be simple, rapid, sensitive, accurate and suitable for the determination of pesticide residues in Pinelliae Rhizoma.