Pesticides are often reported in aquatic environments contamination as being a result of soil leaching and improper disposal of agricultural packages. Advanced oxidation processes have been studied as alternatives to treat such compounds in aqueous media. The aim of this study was to determine the best concentrations of H2O2 and Fe2+ that achieved the most efficient simultaneous degradation of hexazinone and diuron. The central composite design (CCD) and response surface method (RSM) were applied to evaluate and optimize the interactive effects of H2O2 and Fe2+. The dosages of H2O2 and Fe2+ used in the photo-Fenton degradation of an aqueous solution of hexazinone and diuron ranged from 0.09 to 29.1 mmol L-1 and 0.01 to 0.92 mmol L-1, respectively. The response surface revealed low concentrations of H2O2 and Fe2+ to the ideal degradation. These photo-Fenton conditions promoted 100% degradation of hexazinone and diuron and 76% of mineralization in only 30 minutes.