Wolfberry fruit is very popular among consumers because it is rich in nutrients. However, it is vulnerable to diseases caused by insect pest feeding and microbial pathogen infection. Pesticide application is the main approach for controlling wolfberry disease; however, various concerns have been raised regarding chemical residues in foodstuffs and consequent environmental contamination. Matrix interference is a significant challenge in trace analysis. Chromatography, coupled with MS techniques with high sensitivity and selectivity, proved to be a powerful tool for the detection of multi-pesticide residues in complex matrices. The traditional MRM mode has been gradually replaced by the dynamic MRM (dMRM) mode, which could dynamically allocate the retention time window of each target pesticide, significantly adjust the loading cycle time of multiple compounds, and improve the analysis efficiency. The QuEChERS pretreatment method, based on dispersive solid-phase extraction, has been widely used in the detection of pesticide residues in food because it is simple and rapid. In this study, a robust and high-throughput method was established for the simultaneous determination of 118 pesticide residues in wolfberry using the modified QuEChERS method, combined with gas chromatography-triple quadrupole mass spectrometry in dMRM mode. The optimal pretreatment method was determined by comparing the recovery rates obtained with different volumes of added water (5, 10, 15, and 20 mL), different extraction solvents (acetone, n -hexane, acetonitrile, and acetonitrile containing 0.1% formic acid), different extraction temperatures (normal temperature, -18 ℃ for 10 min and 20 min), water absorbent (anhydrous magnesium sulfate), and purification with primary secondary amine (PSA) and octadecylsilane (C 18 ). The results showed that 5 g samples were rehydrated with 10 mL ultrapure water, extracted with 10 mL acetonitrile, frozen at -18 ℃ for 10 min, partitioned with buffer system salt package containing 4.0 g anhydrous magnesium sulfate, 1.0 g sodium chloride, 1.0 g sodium citrate, and 0.5 g disodium citrate, purified up with 800 mg MgSO 4 , 150 mg PSA, and 150 mg C 18 . Pesticides were separated on a capillary column HP-5MS UI (30 m×0.25 mm×0.25 μm), and quantified by a matrix-matched external standard method. The results showed that the 118 pesticides exhibited good linearity in the range from 20 to 640 μg/L, with correlation coefficients R 2 ≥0.9923. The limits of detection and quantification were 0.006-28.344 μg/kg and 0.021-94.480 μg/kg, respectively. The average recoveries at four spiked levels of 0.01, 0.04, 0.10, and 0.20 mg/kg were in the range of 64.97%-126.21%, with relative standard deviations (RSDs) of 0.69%-18.86% ( n =6). The results of the matrix effect showed that 82% of the pesticides exhibited matrix enhancement effects, while others showed matrix inhibition effects. In addition, 9% of the pesticides showed a strong matrix effect, while others showed moderate or weak matrix effects. The matrix effects could be reduced by the matrix-matched standard curve method. The proposed method was employed for the analysis of 10 real samples purchased from local markets. The results demonstrated that pesticides were detected in all the samples, 22 pesticides were detected in total, and 3-12 pesticides were found in a single sample. Chlorpyrifos, fipronil, cypermethrin, pyridaben, and difenoconazole were detected at high detection rates. The captan content in a batch of samples was 1.4066 mg/kg. Thus, the optimized method is simple, fast, accurate, and reliable, and it is suitable for the routine detection and rapid screening of the multi-pesticide residues in wolfberry.