Abstract: Object In order to solve the problems of high alkalinity in return water and strong calcification and scaling in equipment and pipeline caused by lime, Method the response surface analysis of high efficient zinc collector inhibitors, and activators suitable for zinc flotation process with low alkalinity and sulfur inhibition was carried out, a response surface model was established to investigate the interaction of flotation factors in a lead-zinc mine. Result&Conclusion The interaction between copper sulfate and collector EMS-003 had the most significant effect on the grade, the interaction between the amount of copper sulfate and the amount of EMY-30 had the most significant effect on the recovery. A closed-circuit verification test was carried out with the lead tail as the test raw ore. The zinc grade of the lead tail is 42.92% at the condition of the zinc grade of 2.60%, the recovery of zinc concentrate is 98.19%.