In this study, the effects of copper ions (Cu2+) on the sulfidization (Na2S) flotation of malachite was investigated using micro-flotation experiments, zeta-potential measurements, X-ray photoelectron spectroscopy (XPS) analysis, adsorption experiments, and Materials Studio simulation. The results indicated that the flotation recovery of malachite decreased after the pretreatment of the mineral particles with Cu2+ ions prior to the addition of Na2S. The results for zeta-potential measurements and XPS analysis revealed that less sulfide ion species in the pulp solution transferred onto the mineral surface, the sulfidization of malachite surface weakened. The adsorption amount of collector on the mineral surface decreased, and this finding was confirmed by the results of the zeta-potential and adsorption experiments. Materials Studio simulation revealed that the adsorption energy of HS- ions and C4H9OCSS- ions on malachite surface increased after the adding of Cu2+ ion. The competitive adsorption made Cu2+ ions depress sulfidization flotation of malachite, the dissolution of mineral surface affected the adsorption of reagents on it, and decreased the floatability of malachite.