A key strategy for achieving the selective separation of talc and chalcopyrite is the development of chemical depressants with high solubility and strong selectivity. Tannic acid (TA), a polyphenol found in green plants and has good solubility, contains abundant phenolic hydroxyl groups. Moreover, the adsorption mechanism of TA with chalcopyrite and talc was examined after TA was chosen as the separation depressant for chalcopyrite and talc. Single-mineral flotation test results found that at optimal pH and TA and sodium butyl xanthate (SBX) dosages, the flotation recoveries of talc and chalcopyrite were 9% and 92.17%, respectively, and the difference in recovery between them was 83.17%. Results from real ores and artificially mixed minerals tests also confirmed that TA can achieve selective separation of chalcopyrite and talc. Since chalcopyrite has distinct electrochemical properties, the results of atomic force microscope and electrochemical tests demonstrated that there are significant differences in the adsorption behavior of TA on the surface of chalcopyrite and talc. And the adsorption selectivity of SBX on the chalcopyrite surface is better than that of TA on the chalcopyrite surface, which is an important reason for the selective separation of chalcopyrite and talc.