Abstract: The optimization test for the mineral processing process on Au-Cu-Fe polymetallic ore with Cu of 0.12%, Au of 0.12 g/t, S of 2.60% and Fe of 45.52% was studied. There are some problems such as difficulty in copper-sulfur separation, high lime consumption and unsatisfactory separation indexes that exist in the originally designed process of "copper and sulfur bulk flotation-copper and sulfur flotation separation-magnetic separation from the flotation tailings to recover iron". Therefore, the optimization process of "iso-flotation of copper and sulfur-copper and sulfur flotation separation-strengthened flotation of sulfur- magnetic separation from the flotation tailings to recover iron" was proposed based on the problems existing in the original process. Firstly, the selective collector BK306 was adopted to collect copper sulfides and part of easy-floating pyrite from the alkali-free pulp with the iso-flotation process, and then separated them to recover copper and gold. Secondly, the refractory sulfides in the ore were removed by strengthened flotation using activator and strong collector. Finally, the iron was recovered by magnetic separation from the flotation tailings. This optimized process can not only realize the efficient recovery of copper, gold and other valuable metals in the ore and the removal of sulfur, but also significantly reduce the amount of lime required for copper-sulfur separation, and can directly obtain iron concentrate with low content sulfur and better quality in the followed magnetic separation operation. The results of the closed circuit test showed that a copper concentrate could be obtained with Cu grade of 20.10%, Au grade of 15.29 g/t, Cu recovery rate of 68.42% and Au recovery rate of 49.07%; a sulfur concentrate with S content of 30.78% and total sulfur recovery rate of 84.05%; and a iron concentrate with Fe grade of 68.88%, S content of 0.18% and Fe recovery rate of 90.57%. Compared with the originally designed process, the optimized process could increase the copper grade and copper recovery in copper concentrate by 2.49 and 10.25 percentage points, the gold grade and gold recovery in copper concentrate by 5.27 g/t and 17.05 percentage points, and the sulfur recovery rate by 1.78 percentage points, respectively. It realizes efficient and comprehensive recovery of copper, gold, sulfur and iron.