In order to optimize the experimental conditions, the decolorization of Acid Red 3R by electrochemicaloxidation process with catalyst FePMo12-APS-MS4A as packing was performed using response surfacemethodology (RSM). The microstructure and morphology of FePMo12-APS-MS4A were characterizedwith Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electronmicroscopy (SEM) and X-ray fluorescence spectroscopy (XRF). Four control factors were throughlyanalyzed by means of RSM based on Box–Behnken design (BBD). Taking the decolorization efficiency asresponse value, a second order polynomial model was established. The model and analysis stronglyindicated that the cell voltage and airflow caused positive, and the initial pH and inter-electrode distancecaused negative effect on the decolorization efficiency. The interaction between cell voltage and initialpH, initial pH and airflow were also revealed. Under the optimal conditions, the color, COD and TOCremoval efficiency reached 67.3%, 58.4% and 47.9% after 60 min. Liquid chromatography–massspectrometry (LC–MS) analysis revealed that the dye molecule underwent a series of reduction andoxidation steps, including azo bond fracture, desulfonation and denitrogenation. The possiblemechanisms involving in this reaction process were proposed.