The study aimed to evaluate the application of electro-Fenton in the treatment of effluents from the tanning industry in the liming stage. For this purpose, 27 experiments were carried out applying two experimental designs: the central composite design and the Taguchi method (orthogonal design). Current density, electrolysis time, and hydrogen peroxide dosages were analyzed as input parameters, while the evaluated response parameters were: chemical oxygen demand, total suspended solids, and turbidity. The central composite design found removal values of up to 62.13%, 99.87%, and 100.0% of chemical oxygen demand, turbidity, and total suspended solids. Total suspended solids and turbidity were achieved for the Taguchi design up to 87.77%, 91.24%, and 100% removal of chemical oxygen demand. Only the Taguchi design allowed the obtention of a statistically significant model for chemical oxygen demand removal (adjusted R2of 95.16%). The electro-Fenton process allows high removal efficiencies of chemical oxygen demand, turbidity, and total suspended solids. The results presented in the present study allow considering this technology as an alternative for the treatment of tannery effluent; however, further studies are needed to estimate the costs of the process.