Abstract: There are the separation problems of chalcopyrite and galena with similar floatability in bulk concentrate. we studied the inhibition and separation of chalcopyrite and galena by new combination depressant (LY and sodium thiosulfate) under different flotation conditions, and compared them with traditional depressants such as potassium dichromate, carboxymethyl cellulose and sodium sulfite. The results showed that the new combined depressant (LY and sodium thiosulfate) has a good inhibition effect on galena and a weak inhibition effect on chalcopyrite under the condition from natural pH of slurry to weak alkalinity. The artificial mixed ore achieved good separation results. In the closed-circuit verification test of Cu-Pb bulk concentrate, the copper concentrate contain Cu 28.05% with recovery is 84.16%, contain Pb 6.88% with recovery is 3.79%, the lead concentrate contain Pb 65.54% with recovery is 96.21%, contain Cu 1.98% with recovery is 15.84%.