A novel collector S-benzyl-N-ethoxycarbonyl thiocarbamate (BET) was used for selectively recovering galena from a polymetallic sulfide ore, and its flotation performance, structure-property relation and adsorption mechanism to galena were investigated. The raw ore flotation experiment demonstrated that compared with two conventional collectors sodium diethyl dithiocarbamate (SDD) and ammonium dibutyl dithiophosphate (ADD), BET displayed superior flotation performance to galena. Pure mineral flotation and adsorption tests also illustrated that among the three collectors BET possessed the strongest collecting ability and the best selectivity toward galena. The structure-property relation study based on density functional theory (DFT) calculation supported the above conclusion. The adsorption mechanism analysis through DFT calculation indicated that BET was chemisorbed on galena surface via formation of normal covalent bond between carbonyl S atom and Pb atom and back donation covalent bond between carbonyl O atom and Pb atom, which was verified by the result of Fourier Transform Infrared (FTIR) spectra analysis. This new collector exhibits not only strong collecting ability but also good selectivity to galena, and therefore it has wide industrial application prospect.