The purpose of this study was to investigate the effect of astragalus polysaccharides (APSs), active constituents of astragalus, in the treatment of hepatocellular carcinoma (HCC) and their potential as a promising candidate for future anticancer drug development. Astragalus polysaccharide was administered at different doses to HCC H22-bearing mice to investigate their antitumor effects. Results revealed that APS inhibited the growth of H22 cells with a tumor inhibition rate in the APS 400 mg·kg(-1) group of 59.01%. Astragalus polysaccharides significantly increased the spleen and thymus indexes, and also the interleukin (IL) 2, IL-6, and tumor necrosis factor α cytokine concentration in serum, indicating that APS influences immune-regulating properties involved in antitumor activity. In addition, APS increased Bax protein expression and decreased Bcl-2 protein expression; these proteins are apoptosis-regulating factors responsible for cell death or survival. Further development and exploration of APS may enable it to become an effective clinical agent for liver cancer therapy.