In this study the degradation of an azo dye, Methyl Red, which is used in textile industry, using Fenton reaction was studied and optimized by a chemometrics method. Fenton oxidation is one of the Advanced Oxidation Processes (AOPs), in which hydroxyl radicals are generated from Fenton’s reagents (Fe2+, H2O2). The effects of various experimental parameters in this reaction were investigated using Central Composite Design (CCD) method. The experimental design was done at five levels of operating parameters. 28 experiments, with 4 factors and 5 levels for each factor were designed. These factors (or variables) include [Fe2+], [H2O2], [oxalate] and the reaction time. A full-quadratic polynomial equation between the percentage of dye degradation (as the response) and the studied parameters was established. After removing the non-significant terms from the model, response surface method was used to obtain the optimum conditions. The optimum ranges of variables were: 0.1 - 0.4 mM for [Fe2+], 13.5-22 mM for [H2O2], 1.5-2 mM for [Oxalate], and 115-125 min for the reaction time. Also the results of extra experiments showed that these optimized values can be used for real samples and yield to high values for the response.