Abstract: Objective To investigated the anti-tumor effects of megestrol acetate （MA） in combination with arsenic trioxide （As2O3） in hepatocellular carcinoma （HCC）. Methods The HepG2 cells were divided into 4 groups： treated with MA （75 μmol/L） alone， As2O3（1.0 μg/ml）alone， or MA （75 μmol/L） in combination with As2O3（1.0 μg/ml）and negative control group for 24 h. The doses of the drugs were confirmed according to our previous researches. The effect of MA combined with As2O3 on HepG2 cell growth was detected by Cell Counting Kit method （CCK-8） and flow cytometry assay. The expressive effect of X-linked inhibitor of apoptosis protein（XIAP） in HepG2 cells was analyzed with Western blotting. Results CCK-8 assay showed MA combined with As2O3 could significantly inhibit the growth of HepG2 cells compared with MA or As2O3 alone. The apoptotic rate of MA combined with As2O3 group was significantly higher than those of MA or As2O3 group. Compared with MA or As2O3 group， MA combined with As2O3 significantly decreased the expression of apoptosis-related proteins XIAP.