Heterogeneous catalysts with low cost, environmentally friendly, highly effective and ready separation from aqueous solution are highly desirable. Magnetic CuO-Fe3O4 nanoparticles, a type of non-toxic bimetallic transition metal oxide, is a promising heterogeneous catalyst for activation of peroxymonosulfate (PMS) to generate reactive oxygen species (ROS) that has not been previously investigated. In this study, the activation of PMS by CuO-Fe3O4 nanoparticles was evaluated using the degradation of 4-chlorophenol as a model reaction. Several critical factors such as pH, catalyst dosage and PMS concentration were investigated. CuO-Fe3O4/PMS system demonstrated a wide effective pH range to degrade 4-chlorophenol, namely 5.5 to 9.5. With the increase of the catalyst dosage, the degradation efficiency of 4-chlorophenol appeared to increase first and then decrease, that the inflection point was 0.5 g/L. Elevated PMS concentration obviously improved the decomposition of 4-chlorophenol; however, the plateau was reached when the PMS concentration was 8mM. Further increase in PMS concentration would not significantly improve the removal efficiency. Through examining the effects of scavengers and electron spin resonance (ESR) analyses, CuO-Fe3O4 nanoparticles were proven to activate PMS through a non-radical and radical pathway to generate singlet oxygen, sulfate radicals and hydroxyl radicals. Based on results, CuO-Fe3O4 nanoparticles were effective, environmentally friendly and low cost catalysts for efficient activation of PMS. These features make CuO-Fe3O4 nanoparticles a readily available heterogeneous catalyst to activate PMS for refractory organic pollutants degradation in advanced oxidation processes (AOPs).