The peroxymonosulfate (PMS) and peroxydisulfate (PDS) were activated using plain and S-doped MgO (S-MgO) for oxidation of acetaminophen (ACT) in the contaminated water. The findings indicated that S-MgO was more efficient than plain MgO in activating the oxidants and that PMS was much better activated than PDS using SMgO. The complete degradation and significant mineralization (up to 62.4%) of 50 mg/L ACT could be achieved in the S-MgO/PMS process using 1.4 mM PMS within a reaction time of 30 min and 60 min, respectively. Both SO4 center dot- and HO center dot species were simultaneously generated in the S-MgO/PMS process with the contributions of 73.8% and 26.2%, respectively, in the ACT removal attained in the process. ACT removal in the S-MgO/PMS process was not considerably affected by the solution pH between 4 and 10 and the maximum ACT removal of 93.4% was achieved at the neutral condition and optimum PMS to catalyst ratio of 0.07 mML/g. The performance of S-MgO/PMS process for removal of ACT was not affected by the presence of conventional anions in natural waters. The pathway of ACT degradation in the S-MgO/PMS process was proposed based on the Liquid chromatography- mass spectrometry (LC/MS) analysis of the effluent. Accordingly, the S-MgO is a very active catalyst to activate the PMS for simultaneous generation of SO4 center dot- and HO center dot reactive species hence S-MgO/PMS process is an emerging AOP for high rate degrading the pharmaceutical compounds present in contaminated waters.