An analytical method for the simultaneous determination of 322 pesticides and chemical pollutants in Pinellia was established based on optimized dispersive solid phase extraction sample preparation method with gas chromatography-quadruple time of flight mass spectrometry（GC-Q-TOF/MS）.The influences of different extraction solvents,buffer salt systems and purifing agents on the recoveries of pesticides and chemical pollutants were investigsted.The pesticides and chemical pollutants in the samples were extracted with acetonitrile containing 1% acetic acid and acetic acid-sodium acetate，then cleaned up with mixed sorbents and analyzed by GC-Q-TOF/MS under TOF mode.The results showed that 84.2% of the 322 pesticides and chemical pollutants were limited to 5μg/kg and 14.6% of the pesticides and chemical pollutants were screened to 10 μg/kg. The recoveries at the spiked levels of 10，50,100 μg/kg were in the ranges of 70.2%-119.5%,70.6%-119.8% and 70.2%-119.9%, respectively. The relative standard deviations（RSD） were 0.2%-19.7%,0.2%-19.5% and 0.5%-20.0%，respectively. Compared to the original DSPE method,the proposed method was more efficient,rapid,sensitivie and accurate. It is suitable for the rapid screening and quantitative analysis of 322 pesticide residues and chemical pollutants in Pinellia.