Since groundwaters are a major source of drinking water, their pollution with organic contaminants such as methyl tertiary-butyl ether (MTBE) is a very significant issue. Hence, this research investigated the photocatalytic degradation of MTBE in an aqueous solution of TiO2-ZnO-CoO nanoparticle under UV irradiation. In order to optimize photocatalytic degradation, response surface methodology was applied to assess the effects of experimental variables such as catalyst loading, initial concentration of MTBE and pH on the dye removal efficiency. The optimal condition to achieve the best degradation for the initial concentration of 30.58 mg/L of MTBE was found at a pH of 7.68 and a catalyst concentration of 1.68 g/L after 60 min.