A 22 factorial design of experiments complemented with a central point assayed in triplicate was proposed to investigate the influence of initial Fenton’s reagent (H2O2 and Fe2+) concentration on the maximum oxidation of the Ponceau 4R dye in aqueous solution. The reactions took place in batch reactors without (Fenton process) and with (photo-Fenton process) UV irradiation under well-stirred conditions at approximately 25 °C. Based on these preliminary results, the kinetics of color degradation, removal of total organic carbon and consumption of reactants was experimentally investigated for 7200 s at optimal initial concentration of H2O2 and Fe2+. The results show that the Fenton and photo-Fenton process caused approximately 95% of decoloration after only 300 s of reaction and complete color degradation at 7200 s. At this final time of reaction, TOC removals of 97% and approximately 100% were observed when applying Fenton and photo-Fenton conditions, respectively. A toxicity assay revealed that A. salina was not sensitive to the synthetic effluent treated by the photo-Fenton process and diluted with aqueous nutritive solution at 25, 12.5, 10 and 5%. A suggested simplified mechanism involving three elementary reactions was able to reproduce the experimental kinetic results of Fe2+, H2O2 consumption, Fe3+ formation and azo dye degradation. On the whole, the results obtained at the investigated conditions show that the photo-Fenton and Fenton processes are effective processes to achieve TOC reduction and color degradation of Ponceau 4R dye typically found in liquid effluents from the Brazilian confectionary industries.