The degradation of acetaminophen with non-radical based reactive oxidants generated by chloride activated peroxymonosulfate system was investigated. The performance of PMS/Cl- system was also compared with traditional NaClO system in respect of oxidant dosage, pollutant concentration and pH values. Results showed that pseudo-zero-order kinetic model is more suitable to describe the degradation of acetaminophen in PMS/Cl- system nevertheless pseudo-first-order kinetics model is more suitable to NaClO system. A maximum removal of 76.7% was achieved in 120 min when m(APAP)0 was 10 mg/L, [PMS]0 was 0.4 mM and [Cl]0 was 50 mM. In either PMS/Cl- or NaClO system, higher oxidant dosage, lower acetaminophen concentration and lower pH favored removal efficiency. HClO was the main oxidant responsible for organic pollutant removal in both PMS/Cl- and NaClO system, while the HClO was produced more slowly in PMS/Cl- system. In the future, chloride anions would be an alternative choice for elimination of residual oxidant and continuously disinfection in PMS based oxidation processes.