Abstract: OBJECTIVE To develope a multi-residue analytical method for the determination of 156 kinds of pesticide residues in Trichosanthis Fructus by QuEChERS-SPE-UHPLC-MS/MS. METHODS The samples were extracted with acetonitrile containing 1% acetic acid, dehydrated by MgSO₄, simply purified by a mixed cleaning agents of MgSO₄, PSA, and C₁₈, and further cleaned by SPE column(Waters Prime HLB, 3 mL, 60 mg), separated on a Waters Cortecs C₁₈+ column (100 mm×2.1 mm, 1.6 μm) and detected by UHPLC-MS/MS with positive and multiple reaction monitoring mode(MRM). RESULTS The results of all the 156 kinds pesticides showed good linearity in the range of 5-200 μg·L^-1(r<0.995). The average recoveries ranged from 74.9% to 116.4%, with the relative standard deviations(RSDs) from 1.0% to 5.6%, the limits of detection(LODs) of the method were among 0.02-20 μg·kg^-1, and the limits of quantification (LOQs) were among 0.06-50 μg·kg ^-1. CONCLUSION The method is simple, accurate and sensitive, can be used for the determination of multi type pesticides in Trichosanthis Fructus.