Bulk flotation is usually used in the flotation of Cu-Fe sulfide ore, and the subsequent concentrate is difficult to be separated because the minerals have adsorbed the collector. In this paper, flotation tests showed that calcium hypochlorite (Ca(ClO)₂) had a stronger depression effect on pyrite pre-adsorbed sodium butyl xanthate (SBX), while having a negligible depressive effect on chalcopyrite. A copper concentrate with Cu grade of 33.32% and Cu recovery of 94.47% could be obtained from flotation tests of mixed minerals. The depression performance and mechanism of Ca(ClO)₂ were studied by contact angle measurements, Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses, the results suggested that Ca(ClO)₂ can decomposes SBX on the pyrite surface and oxidizes the mineral surface to form hydrophilic substances, which enhances the hydrophilicity of the pyrite surface. In contrast, Ca(ClO)₂ has little effect on chalcopyrite pre-adsorbed SBX, the possible depression model is discussed.