Orange II in aqueous solution was degraded with hydroxyl radicals generated from zerovalent iron (ZVI) and hydrogen peroxide (H2O2) under UV irradiation. Results showed that the introduction of UV light could remarkably enhance the decolorization efficiency of Orange II in the ZVI/H2O2 process (advanced Fenton process, APP). Central composite design (CCD) and the response surface methodology (RSM) were applied to investigate operating condition effects, such as initial pH, ZVI loading, and H2O2 concentration, on the decolorization efficiency at 30 min. The RSM model was derived and the response surface plots were developed based on the results. Moreover, the intermediates during the oxidation process were identified and the degradation pathway was proposed accordingly. After UV-assisted AFP, 68.3% of COD was removed and BODs/COD ratio increased from 0.019 to 0.41, indicating the effluent was more suitable for biodegradation.