AIM: To illustrate the possible role of cell differential agent-Ⅱ (CDA-Ⅱ) in the apoptosis of hepatoma cells induced byarsenic trioxide (As2O3).METHODS: Hepatoma cell lines BEL-7402 and HepG2 weretreated with As2O3 together with CDA-Ⅱ. Cell survivingfraction was determined by MTT assay; morphologicalchanges were observed by immunofluorescence staining ofHoechst 33 258; and cell cycle and the apoptosis index weredetermined by flow cytometry (FCM).RESULTS: Cytotoxity of CDA-Ⅱ was low. Nevertheless, CDA-Ⅱ could strongly potentiate arsenic trioxide-inducedapoptosis. At 1.0 g/L CDA-Ⅱ, IC50 of As2O3 in hepatoma celllines was reduced from 5.0 μmol/L to 1.0 μmol/L (P＜0.01).The potentiation of apoptosis was dependent on the dosageof CDA-Ⅱ. FCM indicated that in hepatoma, cell growth wasinhibited by CDA-Ⅱ at lower concentrations (＜2.0 g/L)primarily by arresting at S and G2 phase, and at higherconcentrations (＞2.0 g/L) apoptotic cell and cell cyclearresting at G1 phaseincreased proportionally. Thecombination of two drugs led to much higher apoptotic rates,as compared with the either drug used alone.CONCLUSION: CDA-Ⅱ can strongly potentiate As2O3-induced apoptosis in hepatoma cells, and two drugs canproduce a significant synergic effect.