Abstract: To achieve simultaneous detection of multiple antiparasitic drugs in multi-matrix oil-control cosmetics, methanol was used as the extraction solvent to perform ultrasonic extraction on water-based, emulsion/cream-based, and oil-based oil-control cosmetic samples. The extract was passed through a 0.22 μm membrane, and the 34 antiparasitic drugs in the filtrate were separated by gradient elution on Thermo Hypersil GOLD aQ column using a mobile phase system consisting of （1） 0.01% （volume fraction, the same below） formic acid solution containing 2 mmol·L⁻¹ ammonium formate and （2） methanol solution containing 2 mmol·L⁻¹ ammonium formate and 0.01% formic acid, ionized by an electrospray ionization source, detected by multiple reaction monitoring （MRM） mode, with quantification by external standard method/matrix-matched external standard method. It was shown that 34 antiparasitic drugs achieved chromatographic peaks within 12 min, showing linear relationships between quantitative ion peak areas and their mass concentrations in definite ranges, and detection limits （3S/N） were found in the range of 7.5−1 500 ng·g⁻¹. Spike recovery tests were conducted on blank water-based, emulsion/cream-based, and oil-based samples, giving recoveries in the range of 70.1%−120%, with RSDs （n=6） of the determined values less 8.0%. The proposed method was applied to the analysis of 50 batches of commercially available samples, and none of the 34 antiparasitic drugs were detected.