Advanced oxidation technology based on PeroxyMonoSulfate (PMS) has become a research hotspot in the field of water treatment. To improve the activation efficiency of PMS, electrochemically assisted spinel type catalyst CoFe2O4 was used to activate PMS and achieve effective degradation of acetaminophen. The influence of single factor on degradation was explored to determine the best degradation process parameters of E/CoFe2O4/PMS system. Results show that under the optimum reaction conditions (DC voltage is 6[Formula: see text]V, the initial mass concentration of acetaminophen is 10[Formula: see text]mg[Formula: see text]L[Formula: see text], the dosage of CoFe2O4 is 0.3[Formula: see text]g[Formula: see text]L[Formula: see text], and the mass concentration of PMS is 1.5[Formula: see text]g[Formula: see text]L[Formula: see text]), the degradation rate of acetaminophen reaches up to 95% within 20[Formula: see text]min. CoFe2O4 catalyst showed a good stability, with only a 12% decrease in acetaminophen degradation after three cycles. Radical quenching tests show that [Formula: see text] and [Formula: see text] played predominant roles in the advanced oxidation process. This work provides a new strategy for more efficiency in PMS activation.