Abstract: A low-alkalinity beneficiation is studied on a high sulfur copper-zinc ore containing 1.13% copper, 1.98% zinc, 17.85% sulfur, 71 g/t silver, 90 g/t cadmium and 21 g/t indium, which the main target minerals are chalcopyrite, sphalerite and pyrite. A gravity concentration is carried out. The results show that at the grinding fineness of −0.074 mm 90%, copper flotation operation using CaO+NaS₂ to inhibit pyrite, taking ZnSO₄+Na₂S₂O₅ as zinc minerals’ inhibitors, and zinc flotation operation using C₉H₈Na₂O₄+CaO to inhibit pyrite. The copper concentrate with 23.59% of Cu grade and 92.85% of Cu recovery rate, which containing 328 g/t Ag, 228 g/t Cd, and 142 g/t In. The zinc concentrate with 45.81% of Zn grade and 80.60% of Zn recovery rate, which containing 796 g/t Ag, 2 000 g/t Cd, and 287 g/t In. The shaking table test obtains sulfur concentrate with a sulfur grade of 42.34% and an operational recovery rate of 68.04%. The synergistic effect of pyrite combination inhibitors reduce the CaO dosage, and the flotation pH value drops below 10. The research results lay a good foundation for the industrial development of this ore.