In copper-gold flotation plants, pyrite which is depressed in copper flotation is often floated subsequently with the addition of sodium sulfide (Na2S) to recover the associated gold. For the first time, this study investigated the role of Na2S responsible for the flotation of pyrite depressed in chalcopyrite flotation through flotation tests and Cyro-XPS (X-ray photoelectron spectroscopy) analyses. It was found that the application of Na2S improved pyrite flotation to the same extent as the application of PAX and the combination of Na2S and PAX further increased pyrite recovery. It is interesting that PAX and Na2S promoted pyrite flotation through different mechanisms. PAX reduced the hydrophilic metal oxidation species and adsorbed on pyrite surface, resulting in the flotation of depressed pyrite. Unlike PAX, Na2S increased the hydrophobicity of pyrite and pyrite flotation by forming elemental sulfur and polysulfide on pyrite surface. The application of PAX and Na2S at the same time further enhanced the hydrophobicity of pyrite and pyrite flotation as a result of the combined actions of PAX and Na2S.