A simple, rapid and efficient method was developed for the high-throughput simultaneously screening and analysis of over 470 pesticides in complex prickly ash samples. This approach involves a single dilution step using ultra-high performance liquid chromatography coupled with Thermo Q-Exactive Focus high-resolution mass spectrometer (UHPLC-Q Exactive MS). The strong matrix effects of prickly ash, which are particularly prominent among agricultural products, necessitated systematic optimization of sample preparation strategies to minimize co-extraction interference for representative pesticides. Multiple parameters such as water volume, extraction solvents, cleanup reagents, and dilution times were carefully adjusted. Moreover, method validation was applied on 477 pesticides in prickly ash matrix, yielding satisfactory results. Notably, 84.5% of the targeted analytes in 10-fold diluted prickly ash extraction solution exhibited a soft matrix effect. Besides, acceptable recoveries at four fortified levels in the range of 74.2%-92.8% with relative standard deviations (RSDs) less than 20%, were obtained. Limit of quantifications (LOQs) of targeted pesticides were ranged from 0.002 to 3.75 mg⋅kg^-1. The proposed method was also successfully applied to monitor the multi-residues of 43 dried market prickly ash samples, further manifesting its grand opportunity in the applications of multiple pesticides residues in spices.