Forward osmosis (FO) was combined with membrane distillation (MD) to treat high salinity hazardous waste landfill leachate. Response surface methodology (RSM) was used to optimize the operating conditions of the FO process by maximizing water flux and removal efficiency of pollutants and minimizing the salt reverse flux. Flow rate of FS (feed solution), flow rate of DS (draw solution) and the concentration of DS were selected as independent variables for incorporation in the Box-Behnken design. Results showed that optimal FS flow rate, DS flow rate and DS concentration for FO stage were 0.87 L/min, 0.31 L/min and 4.82 M, respectively. The optimal temperatures of inlet solution in MD stage were 72.5 +/- 0.5 degrees C and 62.5 +/- 0.5 degrees C when salt concentrations in FS were 25,000 mg/L and 60,000 mg/L (calculated as NaCl). Salt rejection rates were higher than 96% while rejection rates of TOC and TN were higher than 98%. NH4+-N, Hg, As and Sb were completely removed. The results proved optimized FO-MD combined system was a suitable process to treat high salinity hazardous wastewater.