Corticosteroids are important signaling molecules in organisms．Although the content of corticosteroids in human body is very low，they play an important role in regulating physiological activities such as immune system and stress response．In order to establish a rapid quantitative method for the detection of four endogenous corticosteroids，including aldosterone（ALD），cortisol（F），corticosterone（CORT） and cortisone（COR） in human serum by ultra-performance liquid chromatography－tandem mass spectrometry（UPLC－MS/MS）．The sample was pretreated by protein precipitation combined with liquid－liquid extraction（PPT－LLE） using 0.3 mol/L zinc sulfate solution and tert-butyl methyl ether．The separation of target compounds were performed on an ACQUITY UPLC BEH C,18, column（2.1 mm × 100 mm，1.7 μm） using 0.01 mmol/L ammonia－acetonitrile system as mobile phase by gradient elution．The four endogenous corticosteroids were detected by UPLC－MS/MS under multiple reaction monitoring（MRM）mode in positive or negative fast-switching ESI mode，and quantified by the isotope dilution（ID） internal standard method．The results showed that the calibration curves were linear（,r,2,>, 0.995） in the range of 0.05－20 ng/mL for ALD，and 0.02－20 ng/mL for the other analytes．The detection of limit（LOD） and quantitation of limit（LQQ） of ALD wase 20， 50 pg/mL，respectively，the LODs and LOQs of the other analytes were 10， 20 pg/mL，respectively．The absolute extraction recoveries for four corticosteroids were between 55.5% and 90.8%．The method recoveries ranged from 91.0% to 101%，with intra-day relation deviation standards（intra-RSDs） and inter-day RSDs（inter-RSDs） not more than 13% and 18%，respectively．Meanwhile，the matrix effects were in the range of 85.9%－108%．The pretreatment method could purify serum samples significantly and increase the reliability of the detection results．It was easy to realize high-throughput processing without derivatization and complex steps．This method was accurate，rapid，stable and reproducible，and was suitable for the detection of serum endogenous corticosteroids in complex matrices．