This paper used potassium permanganate (KMnO4) as a pyrite depressant to separate pyrite from chalcopyrite. Flotation and contact angle results indicated that pyrite could be depressed by KMnO4 at pH 7, while KMnO4 treated chalcopyrite could be floated by sodium ethylxanthate. Zeta potential analysis revealed that KMnO4 oxidized the pyrite surface, lowering its hydrophobicity. The oxidation products on the pyrite surface were FeO, FeOOH and Fe2(SO4)3 as determined by XPS analyses. These oxidation products were well coated on the pyrite surface, which dramatically lowers the hydrophobicity of pyrite. In contrast, in the case of chalcopyrite, KMnO4 treatment did not generate new oxidation components on its surface, causing chalcopyrite surface to remain hydrophobic and allowing the flotation of chalcopyrite by air bubbles. Thus, pyrite could be efficiently separated from chalcopyrite using KMnO4 as a depressant.