Sodium sulfosalicylate was used for the first time to enhance the sulfidation-flotation of smithsonite. Sodium sulfosalicylate could facilitate the flotation of smithsonite, and increase the flotation recovery by similar to 28%. Inductively coupled plasma analysis indicated that the surface dissolution of the enhanced sulfurized smithsonite decreased significantly. X-ray photoelectron spectral analysis revealed that smithsonite can be sulfurized easily by using sodium sulfide with sodium sulfosalicylate. The effect of sodium sulfosalicylate on zinc-oxide ore flotation has been verified. Compared with the direct sulfidation flotation of zinc-oxide ore, enhanced sulfidation flotation can improve the concentrate grade by 3.83% and the concentrate recovery by 7.63%. Therefore, the addition of sodium sulfosalicylate played a significant role in smithsonite sulfidation, which improves the flotation performance.