Abstract: Lead and zinc are the essential metal raw material in industrial production. With the rapid development of industry, it is difficult to meet the demand of lead and zinc resources for easily sorted lead and zinc sulfide ores. The flotation separation of lead-zinc sulfide ore has always been a research hotspot in the field of mineral processing engineering. However, the high efficient separation and comprehensive utilization of lead-zinc ore are difficult due to the close association of various target minerals in lead-zinc ore and the complex effects of various ions on target minerals. On the basis of previous studies, this paper summarizes and analyzes the main reasons why lead-zinc sulfide ore is difficult to separate. The flotation technology and reagents for the separation of lead-zinc sulfide minerals are described in detail. The prospect of research on separation of lead-zinc sulfide ore is discussed in order to provide reference for high efficient flotation of lead-zinc sulfide ore.