To study the effects of parthenolide on human hepatocellular carcinoma cell line BEL-7402 and explore its possible mechanism, human hepatocellular carcinoma cell line BEL-7402 was cultured in vitro and treated with parthenolide of different concentrations. Cells without addition of parthenolide were used as control. The growth of inhibition of cells induced by various concentrations was analyzed by using the MTT assay. The morphologic changes of apoptosis was observed under an inversion microscope by Giemsa staining. The expression levels of PCNA albumen were measured by means of immunohistochemical methods. Parthenolide can inhibit the proliferation of BEL-7402 cells in vitro in adose-dependent manner. Apoptosis with nuclear chromatin condensation, fragmentation and cell shrinkage were found by means of inversion microscopy. Formation of apoptotic bodies was observed by Giemsa staining. The immunohistochemical results show that the expression of PCNA has been decreased. Parthenolide can inhibit the tumor growing of BEL-7402 cells, and induce the apoptosis of cells. The mechanisms of those functions may be via inhibiting the expression of PCNA.