This study evaluated the influence of experimental factors on reactive red 2 oxidation by the Fenton process using response surface methodology (RSM). Experiments were conducted based on a central composite design (CCD) using operating variables such as H₂O₂, Fe⁺², and reaction time. The responses were evaluated using a second-order polynomial multiple regression model. The analysis of variance (ANOVA) showed a high coefficient of determination (R²) value of more than 0.98. It confirms a satisfactory adjustment of the second-order regression model with the achieved data. H₂O₂ had a significant effect on the removal of RR2 and COD. When the initial concentration of H₂O₂ was 90 mg/l, the efficiency of RR2 removal was 94%. The experimental findings were in close agreement with the model prediction.