Abstract: A rapid screening method for multi-residue of 180 pesticides in Fructus Citri was established by QuEChERS combined with ultra-performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS). An accurate mass database and a high-resolution fragment ion spectrum library were established by optimizing the sample preparation and purification, as well as the search parameters such as the accurate mass extraction window, the retention time window and the absolute peak filter. Moreover, the qualitative and quantitative results of the proposed screening method were verified. The results showed that the linear relationship of the 180 pesticides in Fructus Citri was good within the mass concentration range of 0.005-1 mg/L (r > 0.99), and the screening detection limits (SDLs) of 96.6% of the pesticides were below 0.05 mg/kg. The average recoveries at the three spiked levels (0.02, 0.05, 0.1 mg/kg) were 58%-129%, 68%-131% and 66%-132%, respectively, and the relative standard deviation (RSD) was 0.7%-18% (n=5). Using TOF-MS first-level accurate mass-to-charge ratio screening combined with the confirmation of high-resolution fragment mass spectrometry, the proposed method significantly improved the accuracy of rapid screening for multiple pesticide residues, efficiently reduced the false positive rate, and has universal applicability in the daily monitoring of pesticide residues in Chinese medicinal materials of Fructus Citri.