AIM To investigate the influence of mycophenolate mofetil (MMF) plus adriamycin (ADM) on hepatocellular carcinoma (HCC) cells. METHODS HCC cells were treated with 100 μg/ml of MMF alone (MMF group), 1 μg/mL of adriamycin (ADM group) alone, or a combination of the drugs (MMF + ADM group). We performed an 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay to measure the growth inhibition rate of HCC cells. Flow cytometry was used to determine the percentage of cells in different phases of the cell cycle and the number of apoptotic cells. Hoechst 33258 staining revealed the morphological changes associated with apoptosis in HCC cells. RESULTS The results of MTT assays revealed that monotherapy with ADM or MMF showed inhibition of cell growth, while MMF + ADM therapy afforded an inhibition rate of more than 90% with cell distribution in G1 and G2/M phase greater than that in S phase. MMF + ADM treatment also downregulated Bcl-2 expression markedly. The growth of HCC cells was markedly inhibited and apoptosis was enhanced in all the 3 groups. Compared with other 2 groups, the MMF + ADM group showed more obvious apoptosis of cells. CONCLUSION The MMF plus ADM combination exerts remarkable inhibitory effects on the growth of HCC cells.