This study explores the selective depression mechanism of pyrite by proanthocyanidins (PC) during chalcopyrite-pyrite flotation separation. The selective inhibition effect of inhibitor PC was examined through flotation experiments. The depression mechanism of PC on pyrite was analyzed employing X-ray photoelectron spectroscopy (XPS) analysis, selective adsorption tests, adsorption experiments, contact angle measurement, and zeta potential measurement. The artificial mixed mineral flotation test of chalcopyrite-pyrite at a ratio of 1:12 was conducted under pH 7, PC concentration of 75 mg/L, and PAX concentration of 18.75 mg/L. The copper concentrate exhibited a recovery rate of 88.97%, with a copper grade of 29.43%. The sulfur grade in copper concentrate was 40.35%, and the pyrite recovery rate was 1.97%. PC can be used as a potential depressant of pyrite. adsorption experiments and Zeta potential measurement indicated that PC treatment significantly impeded PAX adsorption on the pyrite surface, as confirmed by XPS test results and Ion adsorption analysis.