This paper focuses on the effect of the venom of the scorpion Heterometrus liangi on the proliferation of human KYSE-510 cell line and the related molecular mechanism. Marked morpho-logical changes in KYSE-510 cells after treatment with scorpion venom were observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Cell appopsis were deternined using flow cytometry. moreover, RT-PCR and Western blot analysis was used to research the different level of p21 and caspase-3 expression. These results suggest that scorpin venom at concentrations of 50–100 ug/mL caused dose- dependent inhibition of KYSE-510 cell proliferation. The ratio of apoptosis and necrosis increased. The effect of venom treated in KYSE-510 cells in p21 gene expression was reinforced, but the caspase-3 gene expression has indistinctive effect. The activity of p21 and caspase-3 protein expression were upregulated after scorpion venom treatment. scorpion venom is to activate the expressions of p21 and caspase-3 protein to cause selective cell apoptosis.