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An ore has a lead grade of 2.56%, a zinc grade of 9.17%, and an associated silver grade of 18.60 g/t in Northwest China, which is a low-lead and high-zinc sulfide ore. In order to solve the problem of serious lead-zinc mixing and high zinc contented in the lead concentrate, a large number of experimental studies have been done on the ore. Combined with process mineralogy, a large number of zinc-inhibiting agents were explored, and finally the composite inhibitor T122 was determined to have a good effect. According to the optimum process conditions determined by conditional test and open-circuit test, the closed-circuit process test was carried out, and the final index of the lead concentrate was 62.22%, the recovery rate was 92.42% and the lead concentrate containing 5.79% zinc. The grade of zinc in zinc concentrate is 57.07% and the recovery rate is 92.45%. The associated elements were well enriched and recovered, and the silver grade in lead concentrate was 390.90 g/t, and the silver recovery rate was 76.50%. Lead, zinc and their associated silver have been well recovered and the comprehensive utilization of mineral resources has been realized.