Cytotoxicity induced by 19 kinds of edible sulfide flavors was investigated in human leukemia HL-60 cells in vitro. The structure-activity relationship was analyzed according to the comparative studies, and the mechanism of tumor cytotoxicity was initially studied. The apoptosis induced by sulfide flavors was determined by DNA fragmentation, and sulfide flavors with strong cytotoxicity were selected. The results showed that difurfuryl disulfide (DFDS), bis (2-methyl-3-furyl) disulfide (BMFDS) and methyl 2 - methyl -3- furyl disulfide (MMFDS) induced stronger cytotoxicity in HL-60 cells than the other flavors. In addition of 10 μM DFDS, BMFDS and MMFDS respectively, cell viabilities decreased by 41.77±1.18%, 53.49±2.88% and 23.63±0.90%, respectively, through using cell counting kit-8 (CCK-8). The number of sulfur atoms and furyl played important roles in cytotoxicity of HL-60 cells. Pretreatment of HL-60 cells with antioxidants of GSH and NAC showed that the antioxidants had significant protective effect on cytotoxicity induced by BMFDS and DFDS in HL-60 cells, which further suggested that BMFDS and DFDS might induce cytotoxicity by ROS production in HL-60 cells.