The optimization of the photocatalytic degradation of a carcinogen pesticide, imazalil, was carried out in an aqueous solution using TiO2 as photocatalyst under UV irradiation in the presence of persulfate. Persulfate plays a double role; an electron scavenger and it promotes the formation of sulfate radicals which allow accelerating the removal of imazalil. For the optimization, experimental design was used based on the surface response methodology; it was applied to assess the individual and interaction effects of several operating parameters (pH, TiO2 concentration, pesticide concentration and persulfate concentration) on the treatment efficiency (90% of pesticide removal time). Based on the experimental design data, a semi-empirical expression was obtained, permitting to predict and to optimize the pesticide removal time. This model was very consistent with experimental results (correlation factor: 99.15%). The strongest interactions between the parameters assessed were pH/[K2S2O8] and [Imazalil]/[K2S2O8]. Optimal experimental conditions found for imazalil (25 mg L-1) removal were acidic pH 3-4, persulfate concentration (approximate to 2.5 g L-1) and TiO2 loading (2.5 g L-1). By using tert-butanol as hydroxyl radical scavenger, it was found that sulfate radicals were predominant at acidic pH and as the pH increases the hydroxyl radicals are more and more produced. The experimental design allows obtaining the maximum of efficiency with the minimum amount of persulfate. This work demonstrates well the utility and benefits of the experimental design approach for screening and modeling the reaction parameters. Furthermore, it contributes significantly to the improvement and better understanding of photocatalytic processes using oxidants. (C) 2012 Elsevier B.V. All rights reserved.