Flotation is a technique for mineral separation based on differences in surface hydrophobicity, processing around 10 billion tons of minerals globally each year. Flotation reagents are central to mineral flotation technology. The functional group structures of organic flotation reagents primarily consist of four ligand atoms: N, O, P, and S. After extensive development over centuries, the combinations of these atoms have been fully explored, leading to a bottleneck in new flotation reagent structures, with few novel formulations reported. This study is the first to identify selenium (Se) as a viable ligand in flotation reagents. We utilized contact angle measurements, SEM, FTIR, Raman spectroscopy, TOF-SIMS, XPS, and DFT simulations to examine the interactions between six seleniumbased organic compounds and chalcopyrite surfaces, confirming that Se can coordinate with Cu+ ions. Actual ore flotation experiments demonstrated that benzeneselenol and dibenzyl diselenide achieved superior flotation performance at lower dosages compared to the traditional collector IPETC for copper sulfide ores. This research addresses the limitations of conventional ligand atoms in flotation reagents by introducing Se, expanding potential functional group structures. This advancement provides more opportunities for designing efficient and environmentally friendly flotation agents and introduces novel concepts for using selenium-based organic compounds as metal complexes.