Abstract: The content of magnesium silicate gangue minerals in Jinchuan sulfide copper-nickel ore is high. It affects the enrichment of nickel and copper in concentrates through heterogeneous condensation and mechanical entrainment after grinding. Related researches and foreign industrial practices have proved that acidic medium flotation can promote the decomposition of magnesium silicate gangue minerals, which significantly improved the recovery of useful minerals in copper-nickel sulfide ore and reduced the content of magnesium oxide in concentrates. At present, however, there are few researches on the suitable reagent system for the acidic medium flotation of sulfide minerals in China. To solve this issue, feed of the second stage processing production line of the third flotation plant of Jinchuan Group Co. (Ni and Cu grade of ore was 0.42% and 0.32% respectively) was regarded as the research object. The open circuit flotation tests studied the new reagent system suitable for the acid medium, and compared and analyzed the performance of different frothers by using the foam tester. Under acid flotation condition (pH value = 4), with sodium isobutyl xanthanate (NaIBX) as the collector, O-isopropyl-N-ethylthiocarbamate (Z-200) as the co-collector and terpineol as the frother, after one roughing, two cleaning and two scavenging, the recovery of Ni and Cu are 58.92%, 45.60% and the grade of Ni and Cu are 3.54%, 2.03% respectively. Compared with comparative system (according with industrial process), the recovery of Ni and Cu are increased by 7.54%, 24.40% and the grade of Cu is increased by 0.70%. The new reagent system significantly improved the comprehensive utilization rate of copper-nickel sulfide resources in Jinchuan.