The effects of the operating conditions, including the applied pressure, feed organic concentration, and recirculation flowrate along the TiO2-coated ceramic membrane, on the normalized membrane permeability and organic removal efficiency were systematically investigated by operating a photocatalytic membrane reactor (PMR). Response surface methodology (RSM) was conducted to better understand the interactive effect of operational conditions as well as their individual and combined effects to control membrane performance. Our results showed that the applied pressure and feed organic concentration, as single parameter, affected the normalized membrane permeability and organic removal efficiency more dominantly than the recirculation flowrate. The polynomial performance equations generated by RSM successfully predicted the membrane performance of the PMR. The responses to the normalized membrane permeability and organic removal efficiency with respect to the operational conditions were less sensitive to any combination of operational conditions than to their individual impacts. The combined effects of the operating conditions were less pronounced in promoting the catalytic performance of organic contaminants on the TiO2 surface. Our RSM analysis based on experimental observations designed by Box–Behnken Design (BBD) suggested that 1.3 bar of applied pressure, 44 mg/L of feed organic dye concentration and 0.8 L/min as recirculation flowrate as optimum conditions achieved more than 98% of organic removal efficiency and less than 5% of decline in normalized membrane permeability. This research shows that the RSM provides effective tool to optimize operational conditions to determine fouling rate and organic removal in PMR.