Hyper-crosslinked polystyrene is proposed for the purification of extracts after sample preparation by the QuEChERS method using multicomponent dispersive solid-phase extraction in the determination of residues of 19 pesticides in wheat grains by gas chromatography with tandem mass spectrometry detection. Sample preparation included extraction with water and acetonitrile followed by the purification of the extracts using hyper-crosslinked polystyrene. The method ensures the quantitative isolation of pesticides (recovery range from 66 to 100%). Pesticides are identified by selected transitions in the multiple reaction monitoring mode. The determination is performed using the matrix calibration method, the limits of detection and quantification are 0.03–0.3 and 0.1–1.0 μg/kg, respectively. An analysis of contaminated wheat samples show that the results satisfactorily coincide with the data obtained by the classical QuEChERS method in determining pesticide residues in agricultural products.