The study examined the effectiveness of the modified photo-Fenton (UV-vis/ferrioxalate/H2O2) process in treatment of an antibiotic aqueous solution. The optimum operating conditions for the treatment of a 300 mg/L antibiotic aqueous solution (150 mg/L of amoxicillin and 150 mg/L of cloxacillin) were obtained by using the central composite design of the response surface methodology. Under the optimum operating conditions (H2O2/chemical oxygen demand (COD) molar ratio 2.75, H2O2/Fe3+ molar ratio 75, H2O2/C2H2O4 molar ratio 37.5, reaction time 90 min and pH 3), 78.37, 45.94, and 52.30 removal of COD, NH3-N, and TOC, respectively, were achieved and the biodegradability (biochemical oxygen demand(BOD)5/COD ratio) improved from 0 to 0.35. Model prediction and experimental removal efficiency were in agreement with < 5 error. The modified photo-Fenton process is effective in pretreatment of the antibiotic aqueous solution for biological treatment. © 2013 Balaban Desalination Publications.