Disperse Red 60 simulated polyester alcoholysis liquid decoloration by electro-Fenton with Fe3O4 catalyst was studied. The inﬂuences of the main operating parameters such as catalyst dosage (0.3–0.9 g/L), current density (60–120 mA/cm2) and pH (1–7) were optimized by response surface methodology (RSM) based on Box–Behnken surface statistical design (BBD). In optimal conditions, the initial concentration of 25 mg/L disperse red polyester alcoholysis liquid was catalyzed by 0.6 g/L Fe3O4, and the decoloration efficiency was 97.18% with the current density of 90 mA/cm2 and initial pH of 4.6. There was a relative error of 1.18% with the predicted model when the predictive value was 98.25% under the same conditions. In addition, ultraviolet-visible absorption spectra (UV-Vis), Fourier transform infrared spectroscopy (FTIR) and thermogravimetric analysis (TGA) were used to study the degradation mechanism during decoloration. The intermediates were identiﬁed and the proposed degradation pathways were investigated by liquid chromatography-mass spectrometry (LC-MS) analysis.