Abstract: In this article, the low-grade barite in Guizhou was taken as the research object, with 42.93% BaSO₄ and 1.39% ZnS in the original ore. After pre-dezincification through “one roughing and one scavenging”, the dezincification tailings were used as raw materials, and the self-developed high-efficiency collector EM507 and “one roughing, one scavenging and four cleaning” flotation process were adopted, the closed-circuit test could be obtained BaSO₄ of 91.05%, Zn of 0.036%, BaSO₄ recovery of 96.69% of the barite concentrates. The true specific gravity of the concentrate was 4.41 and the whiteness was 55.49%, which could reach the standard of first grade barite for chemical industry. The research results were expected to make economic and efficient use of the zinc-containing low-grade barite in Guizhou.