Zinc sulfate is a commonly used selective depressant for zinc sulfide minerals, and a mixture of ZnSO4 and Na2CO3 is an effective combined inhibitor for talc. This study indicated that only using ZnSO4 could inhibit talc in chalcopyrite flotation and its depression mechanism was investigated. Microflotation tests indicated that ZnSO4 could selectively depress talc flotation when the pH was greater than about 7.5. Zeta-potential measurements indicated that ZnSO4 could change the zeta-potentials of talc but had a slight influence on that of chalcopyrite. Solution chemistry study of ZnSO4 solution indicated that when the pH was greater than about 7, the hydrophilic precipitate of zinc hydroxide generated. Fourier transform infrared spectra (FTIR) measurements and X-ray photoelectron spectroscopy (XPS) analysis indicated that the precipitate of zinc hydroxide could adsorb on talc surfaces, and Mg2+ ions of talc surfaces may be the active sites which interacted with the precipitate. These results demonstrated that the precipitate of zinc hydroxide was the species of ZnSO4 solution which inhibited talc flotation. The adsorption morphology of the precipitate on talc surfaces was observed by AFM, suggesting that the adsorption of the precipitate roughened the talc surfaces.