Acetaminophen (ACT) was used as the target pollutant in this study. The effects of Fenton's reagent by electro-Fenton (EF) and photoelectro-Fenton (PEF) processes were investigated to determine the ACT degradation. At pH 3, increasing the Fe2+ and H2O2 concentrations to maximum (from 0.01 to 0.10 mM and 5 to 25 mM), leads to increase on the hydroxyl radicals which improved the degradation efficiency of ACT. The results of Box-Benhken design show that Fe2+ and H2O2 positively affect the degradation efficiency of ACT, while pH was the reverse. The maximum ACT degradation efficiency for EF and PEF processes was 99% at 40 min under pH 3, initial [Fe2+] of 0.10 mM and initial [H2O2] of 25 mM. Result shows that H2O2 to Fe2+ molar ratio obviously affect acetaminophen degradation of both EF and PEF processes. Added UVA irradiation for first stage (PEFi/EFi) increased the acetaminophen degradation, when H2O2 to Fe2+ molar ratio was less than 300. On the contrary, applied UVA efficiency for second stage (PEFk/EFk) was decreased, because there was few hydrogen peroxide available in the solution. (C) 2013 Elsevier B.V. All rights reserved.