The Fenton process was used to increase the biodegradability of refinery wastewater. Initially, effects of reaction time, H2O2/COD and H2O2/Fe2+ molar ratios were investigated and biodegradability of wastewater was determined in terms of the BOD5/COD ratio. Preliminary results showed that the Fenton process was able to improve wastewater biodegradability from 0. 27 to 0. 43. Subsequently, the process was optimized by using response surface methodology based on a five-level central composite design. Adequacy and significance of results were analyzed in analysis of variance. The quadratic model was found to be significant to give less than 0. 05 probability of error. The model was fit with data based on insignificant of lack-of-fit test at values of 0. 93. The high R2 and Adj. R2 (0. 95 and 0. 91) indicates satisfactory adjustment of quadratic model to experimental data. Based on optimized conditions, wastewater biodegradability improved to 0. 44 via H2O2/COD and H2O2/Fe2+ molar ratios of 2. 8 and 4 within 71 minutes reaction time. © 2013 Korean Institute of Chemical Engineers, Seoul, Korea.