In the present study, the feasibility of using sulfate radicals generated by coupling ferrous ions and persulfate as a transition metal and oxidant, respectively, was investigated for the removal of Microcystis aeruginosa. The results show that the Fe2+/S2O82− process was effective for the removal of Microcystis aeruginosa and influenced by operating parameters, such as the mass ratio of Fe2+ and S2O82−, persulfate dosage, initial solution pH, and reaction time. The mass ratio of Fe2+ and S2O82− and concentration of persulfate noticeably impacted the Microcystis aeruginosa removal efficiency, with the mass ratio of Fe2+ and S2O82− having a more significant effect than the persulfate dosage. The chlorophyll a removal rate of Microcystis aeruginosa reached 95.38% under the following optimum orthogonal conditions: a mass ratio of Na2S2O8/FeSO4 of 2:1, a Na2S2O8 dosage of 25mg/L, a pH of 4, and a reaction time of 60min. Both sulfate and hydroxyl radicals generated from the Fe2+-activated persulfate system were responsible for the inhibition of Microcystis aeruginosa cell growth and reproduction through destruction of the cellular structure, degradation of cell inclusions and inhibition of photosynthesis. This study indicated that the application of Fe2+-activated persulfate oxidation is a feasible method for treating cyanobacterial blooms.