Objective:To explore the combination effects of all-trans retinoic acid(ATRA)with interferon-gamma(IFN-γ)on human hepatocarcinoma cell line SMMC-7721 and the mechanism of action.Methods:SMMC-7721 cells were divided into treated group and control group.The cells were treated with ATRA or ATRA+IFN-γ in the former and added with PBS in the latter.The inhibition rate of SMMC-7721 cell proliferation was detected by MTT,the cell change in morphology was observed by electron microscope.The apoptosis was detected by flow cytometry and the expression changes of nuclear factor-kappaB(NF-κB)was analyzed by West blotting when the SMMC-7721 cells were treated with ATRA and IFN-γ.Results:The SMMC-7721 cell proliferation was suppressed and apoptosis was induced after the cells were treated with ATRA treatment,and these effects were enhanced when ATRA was combined with IFN-γ.The expression of NF-κB was reduced after SMMC-7721 cell was treated with ATRA,and reduced significantly when the cells were treated with the combination of ATRA and IFN-γ.Conclusion:IFN-γ can enhance the inhibiting effects of ATRA on cell proliferation and inducing apoptosis on SMMC-7721 cell and these effects might be mediated by inhibiting the expression of NF-κB.