Abstract: A gas-chromatography-tandem mass spectrometry (GC-MS/MS) method was established for simultaneous determination of 99 pesticide residues in four matrices, including dried red dates, apricots, grapes and pears. Samples were extracted with acetonitrile, salted out by sodium chloride, and centrifuged. The supernatant was purified by dispersive solid phase extraction (d-SPE), concentrated and dissolved in acetone to volume, and determined by GC-MS/MS. Three cleanup approaches were compared, including solid phase extraction (SPE) with Carb/NH₂ SPE column, dispersive solid phase extraction (d-SPE) with NH₂ + C₁₈ + GCB, and d-SPE with primary-secondary amine (PSA) + C₁₈ + GCB. The results showed that d-SPE with PSA + C₁₈ + GCB were favorable than the other two approaches. Applying the optimized method, targeted compounds were quantified by the matrix-matched external standard calibration method. The calibration curves in four matrices were in the range of 0.005-0.5 mg/L with good coefficient (R² ≥ 0.9915), and the limits of quantification (LOQs) ranged from 0.01 to 0.025 mg/kg. At four spiked levels of 0.01, 0.025, 0.05, and 0.1 mg/kg, the average recoveries of 95 pesticides (96% of total) were 70%-120% and the relative standard deviations (RSD) were 0.3%-20%. The method is simple and efficient, and the sensitivity, accuracy, and precision can meet the routine testing requirements. It is suitable for the simultaneous determination of multiple pesticide residues in the above four fruit matrices.