A novel method was developed for the simultaneous rapid determination of 81 illegally added glucocorticoids (GCs) in cosmetics using dispersive-solid phase extraction (d-SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The analytes were extracted by acetonitrile after dispersing with water, and then purified using the C18 and primary secondary amine (PSA). The chromatographic separations were performed on a Poroshell 120 PFP column (100 mm×2.1 mm, 2.7 μ m) under multiple chromatographic retention modes. Acetonitrile and 0.2% (v/v) acetic acid aqueous solution were used as mobile phases with gradient elution, and all the 10 groups of isomers were baseline separated. The qualitative identification and quantitative analysis of the 81 GCs were operated in the electrospray ionization positive mode using dynamic multiple reaction monitoring (DMRM). The 81 GCs finally were quantified by internal standard method. The correlation coefficients of linear calibration curves were greater than 0.99 in the corresponding mass concentration ranges. The average recoveries of the 81 GCs at three spiked levels ranged from 68.8% to 105.3% with relative standard deviations (RSDs) of 2.9%-13.1% (n=6). The LODs (S/N ≥ 3) and LOQs (S/N ≥ 10) were 0.002-0.006 μ g/g and 0.005-0.020 μ g/g, respectively. A number of 137 cosmetic samples submitted by customers were screened. Sixteen positive samples were found, and the contents of GCs were from 16.9 μ g/g to 158 μ g/g. The results showed that the new method is simple, rapid, sensitive and reliable, and it is suitable for qualitative and quantitative screening analysis of the 81 GCs in cosmetics simultaneously.