Abstract: An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the simultaneous determination of 13 prohibited ingredients (such as econazole) in cosmetics. The samples were dispersed with saturated sodium chloride solution, extracted with acetonitrile under ultrasonication, and the supernatant was diluted with water. Separation was performed on a Waters ACQUITY UPLC HSS T3 column (2.1 mm × 100 mm, 1.8 µm) using a gradient elution with 0.1% formic acid and acetonitrile as the mobile phase. Positive and negative ion scanning was applied in multiple reaction monitoring (MRM) mode for detection, and quantitative determination was conducted via a matrix-matched standard curve with the external standard method. The results demonstrated excellent linearity for the 13 prohibited ingredients in water-based, emulsion, and cream matrices, with correlation coefficients (r) exceeding 0.995. The limits of detection and quantitation were 0.2 ~ 2 μg/kg and 0.6 ~ 6 μg/kg, respectively. The recoveries were 77.50% ~ 120.00%, and the relative standard deviations were 1.3% ~ 7.3%. This method offers simple pretreatment, high sensitivity, accuracy, and reliability, and is applicable for efficient and accurate detection of 13 prohibited ingredients in cosmetics.