Abstract Solamargine possessed a potent cytotoxicity to human hepatocyte (Hep3B) and normal skin fibroblast. The inhibition curves of solamargine to the both cells were essentially overlapped, suggesting a parallel effect for the cell death. To define mechanism of cytotoxicity of solamargine, the changes of morphology and DNA content in cells were studied. A sub-G 1cell stage was drastically increased after 3-h incubation with solamargine. The results evidence that solamargine arises cell death by apoptosis. In addition, the gene expression of TNFR I were up-regulated within 30 min of solamargine treatment. Since TNF Receptor I has been involved in apoptosis, the overexpression of TNF receptor I may be related with the mechanism of cytotoxicity of solamargine. This communication is the first report that a component of Chinese herbs triggers gene expression of human TNFR I which may lead to cell apoptosis.