In this study, the removal of acetaminophen (ACT) in the Fe2+/persulfate system has been comprehensively evaluated. A kinetic model has been established based on the principal reactions. Good accordance between the experimental data and the predicted results under different operational conditions including molar ratio of Fe2+ to persulfate, initial pH, initial ACT concentration, the presence of chloride, under natural water matrices and the mixture of ACT, amoxicillin and pyridine, evidences the validity of the proposed kinetic model. The rate constants for ACT reacting with SO4 center dot- and HO center dot were determined as (1.80 +/- 0.17) x 10(9) M-1 s(-1) and (3.26 +/- 0.41) x 10(9) M-1 s(-1), respectively. SO4 center dot- was evidenced to be the primary radical accounting for ACT removal through both kinetic model calculation and the scavenging results, using either methanol or tert-butyl alcohol. The optimum molar ratio of Fe2+ to persulfate for ACT removal was determined to be 5:4. The removal rate of ACT was little affected by initial pH due to the rapid decrease of solution pH caused by the hydrolysis of iron ions. Cl- has a dual effect on the removal of ACT, and Cl-2(center dot-) rather than SO4 center dot- is proposed as the dominant radical for ACT removal at 10.0 mM Cl-. Possible degradation pathways are also proposed based on the detected intermediates.