A series of new pyrazole derivatives from emodin synthesized in our lab have been shown to have much stronger cytotoxicity than emodin against various tumor cell lines. This study was to examine the apoptosis-inducing activity of these new emodin derivatives in human hepatocellular carcinoma HepG2 cell culture for a better understanding of their cytotoxic effects on the cancer cells. Several major events in the induction of cell apoptosis, nuclear chromatin condensation, DNA fragmentation, caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage were detected in the cells after treatment with the compounds at various concentrations. Of the seven emodin derivatives tested at a dose of 10 microM and within a treatment period of 24 h, only compounds 1 and 3 effectively induced all these apoptotic events in the cancer cells. The apoptosis-inducing activity of the compounds showed a positive correlation to their cytotoxic activity, suggesting a close connection between the growth inhibition and apoptosis induction of the cancer cells by these pyrazole emodin derivatives.