Abstract: A method for the quantitative analysis of 50 prohibited drugs in cosmetics by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) has been developed. The samples were extracted with acetonitrile (containing 0.5% formic acid) by ultrasonic extraction, freezing centrifuged, and the supernatant was fixed in an ethylenediaminetetraacetic acid disodium salt solution (2 mg/L). Then the analytes were separated using a CAPCELL CORE C18 chromatographic column with mobile phase A (methanol) and mobile phase B (0.1% formic acid in water) by gradient elution, finally analyzed by positive and negative mode with electrospray ion source (ESI). The data were acquired by a multiple reactions monitoring (MRM) mode. In the mass concentration range of 10~100 ng/mL, 50 prohibited drugs showed good linear relationship with all their correlation coefficients (r) more than 0.991 0. The detection limits were within 0.05~33 ng/g, and the quantification limits were within 0.15~99 ng/g. The average recovery rates of the samples were within 87.2%~109.7% with the relative standard deviations（RSD) not greater than 10.0%. The method is simple, sensitive and reproducible, and can be used for the rapid and accurate qualitative screening and quantitative determination of 50 prohibited drugs in cosmetics.