COD/sulfate ratio and hydraulic residence time (HRT), both of which influence sulfate loadings jointly, are recognized as the most two important affecting factors for sulfate removal and bioelectricity generation in the novel up-flow anaerobic sludge blanket reactor-microbial fuel cell (UASB-MFC) integrated system. The response surface methodology (RSM) was employed for the optimization of this system and the optimum condition with COD/sulfate ratio of 2.3 and HRT of 54.3 h was obtained with the target of maximizing the power output. In terms of maximizing the total sulfate removal efficiency, the obtained optimum condition was COD/sulfate ratio of 3.7 and HRT of 55.6 h. Experimental results indicated the undistorted simulation and reliable optimized results. These demonstrated that RSM was effective to evaluate and optimize the UASB-MFC system for sulfate removal and energy recovery, providing a promising guide to further improvement of the system for potential applications. (C) 2012 Elsevier Ltd. All rights reserved.