Abstract: A database of 460 pesticide residues was established based on gas chromatography-tandem mass spectrometry (GC-MS/MS). Being combined with QuEChERS sample preparation technology, it was used for rapid and high-throughput screening of pesticide residues in Chinese herbal medicines. The samples were extracted with 0.1% acetic acid-acetonitrile, cleaned-up by dispersive solid phase extraction with PSA + C₁₈ after salting out with sodium chloride, and then determined by GC-MS/MS. The results showed that the limits of quantification (LOQs) of 421 pesticides in 5 types of Chinese herbal medicine matrices, including rhizome, mosaic, seed, whole grass and bark, were between 0.006 and 221 μg/kg, of which more than 80% of them were less than 50 μg/kg. At the spiking level of 100 μg/kg, the recoveries of more than 72% pesticides were between 60%-120%, and the precision of more than 77% pesticides was within 20%. The method has the advantages of simplicity, rapidity and high throughput, and has achieved the simultaneous detection of more than 400 pesticide residues in one injection. A total of 72 pesticide residues were detected in 215 batches of commercially available samples, among which, the detection rates and the concentrations of chlorpyrifos and cyhalothrin were both high, and their potential risks on quality and safety should be concerned.