In this study, the TiO2-ZnO-CuO nanoparticles were primed by sol-gel method characterized by X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM), for degradation of MTBE solution in water. The effectiveness of the treatment method applied for the degradation of MTBE based on an advanced photocatalytic oxidation process was investigated. The three various key parameters were optimized using response surface modeling namely: pH, TiO2-ZnO-CuO concentration and the initial MTBE concentrations. The optimized values were obtained at the PH (7), TiO2-ZnO-CuO concentration (1.49 g/L), and the initial MTBE concentration (31.46 mg/L). Finally, kinetics reaction of degradtion MTBE was carried in the optimum conditions.