Process mineralogical analysis indicates that the valuable minerals in a low-grade lead-zinc sulfide ore in southern China are galena, sphalerite and associated silver minerals, while other metal sulfides are predominantly pyrrhotite and pyrite. To achieve the efficient comprehensive utilization of lead, zinc and silver resources, systematic flotation tests were conducted on the ore. Through conditional tests on grinding fineness, lead flotation and zinc flotation, the suitable grinding conditions and reagent regime were determined. A preferential lead-zinc flotation flowsheet was adopted, in which both the lead and zinc flotation circuits consist of one roughing, two cleanings and one scavenging stage. Closed-circuit test results demonstrate that at a grinding fineness of 56.6% passing -0.074 mm, a lead concentrate with a Pb grade of 65.08% and a recovery of 91.32%, alongside an Ag grade of 1 323.80 g/t and a recovery of 79.28% was obtained. Additionally, a zinc concentrates with a Zn grade of 41.70% and a recovery of 85.96% was produced. This process realizes the effective recovery of valuable elements from the low-grade Pb-Zn-Ag sulfide ore, providing a reference for the development and utilization of similar resources.