•The APAP degradation exhibited a pseudo-first-order kinetics pattern well.•The Fe3O4 was stable without significant leaching of iron to water during reaction.•XPS and EPR results show that Fe2+Fe3+ cycle was answerable for radical generation.•The removal of APAP is a result of oxidation due to both OH• and SO4−•. Magnetic nano-scaled particles Fe3O4 were studied for the activation of peroxymonosulfate (PMS) to generate active radicals for degradation of acetaminophen (APAP) in water. The Fe3O4 MNPs were found to effectively catalyze PMS for removal of APAP, and the reactions well followed a pseudo-first-order kinetics pattern (R2>0.95). Within 120min, approximately 75% of 10ppm APAP was accomplished by 0.2mM PMS in the presence of 0.8g/L Fe3O4 MNPs with little Fe3+ leaching (<4μg/L). Higher Fe3O4 MNP dose, lower initial APAP concentration, neutral pH, and higher reaction temperature favored the APAP degradation. The production of sulfate radicals and hydroxyl radicals was validated through two ways: (1) indirectly from the scavenging tests with scavenging agents, tert-butyl alcohol (TBA) and ethanol (EtOH); (2) directly from the electron paramagnetic resonance (ESR) tests with 0.1M 5,5-dimethyl-1-pyrrolidine N-oxide (DMPO). Plausible mechanisms on the radical generation from Fe3O4 MNP activation of PMS are proposed based on the results of radical identification tests and XPS analysis. It appeared that Fe2+Fe3+ on the catalyst surface was responsible for the radical generation. The results demonstrated that Fe3O4 MNPs activated PMS is a promising technology for water pollution caused by contaminants such as pharmaceuticals.