Abstract: The separation of Cu-Zn polymetallic sulfide by flotation has been a difficult and well-researched topic in the field of mineral processing. One of the important reasons why it is difficult to separate Cu and Zn is the presence of a large amount of copper ions in the pulp, which results in the unavoidable activation of sphalerite. The key to solving this difficulty is the development of a high-selectivity depressor for sphalerite. Sodium dimethyl dithiocarbamate (SDD, C₃H₆NS₂Na) is the lowest homologue of dialkyldithiocarbamate salts, and it has the shortest hydrophobic group (-CH₃) in its molecular structure with weak hydrophobicity. In preliminary exploration experiments, it was found that SDD has good selectivity for Cu-Zn sulfide flotation and can achieve better separation performance than conventional depressors. However, the depression mechanism is not very clear. In this work, the depression effect of SDD on copper-activated sphalerite was revealed by conducting a monomineral flotation test. Based on the results of this test, the competitive adsorption mechanism of SDD and BX on the surface of copper-activated sphalerite was further studied by conducting the Zeta potential test, LEIS (local AC impedance) test of Versa STAT electrochemical workstation, and frontal orbital theory calculation. The flotation results show that the SDD can effectively act as a depressant in copper-zinc separation. Sphalerite is depressed effectively in the presence of SDD, while chalcopyrite is not depressed. In addition, SDD has the characteristics of small dosage and high sensitivity. Under the optimum conditions with pH of 10 and SDD dosage of 4.0×10^-5 mol·L^-1, the recovery of copper-activated sphalerite can be reduced to 16.59%, while the recovery of chalcopyrite is 81.64%. Analysis of the results of the Zeta potential test and LEIS show that SDD can not only occupy the activation site of copper-activated sphalerite surface but also afford better adsorption capacity than BX, which greatly reduces the adsorption of BX on the surface of sphalerite. As a result, SDD shows a good depression effect for copper-activated sphalerite. The frontier orbital calculations further confirm that SDD is superior to BX in its ability to interact with minerals.