Chemical synthetic pharmaceutical wastewater must be pretreated before traditional biological treatment to improve the biodegradability of pollutants due to their high concentration and complex composition. This study investigated O-3 and O-3/H2O2 systems to pretreat hydrocortisone wastewater. The optimum treatment efficiency of the O-3 system was achieved under pH value of 5.76, dosage of O-3 of 217.5 mg/L, and reaction time of 90 min. The removal efficiency of chemical oxygen demand (COD) and total organic carbon (TOC) was 94% and 92%, respectively. The ratio of biochemical oxygen demand (BOD) and COD (B/C) increased from 0.066 to 0.310. Moreover, the optimum H2O2/O-3 molar ratio was 0.3 with the optimum pH of 3, and reaction time was reduced to 15 min to reach COD removal efficiency of 67.3% in the O-3/H2O2 oxidation system. Interestingly, isobutanol was assumed to be a good hydroxyl radical trapping agent due to the great decrease of Fenton reagent reaction rate constant. By comparing two different kinetic models, oxidation mechanism could be interpreted by the pseudo first-order kinetic model with the high correlation coefficient R-2 above 0.9787. It can be concluded that ozonation system was controlled by both direct oxidation and free radical oxidation, and particularly the later one played a dominant role.