The immunoregulatory and antioxidant activities of polyphenols from black tea on H22-bearing mice were investigated. These mice were simultaneously administrated by gavage with black tea polyphenols at different dosages [250 mg/（kg·d） and 500 mg/（kg·d）] for 35 days and inoculated with H22 cells on day 14. After the last administration, the tumor inhibition rate, immune organ indexes, proliferation ability of splenocytes（T and B lymphocytes）, splenic NK cell killing activity and phagocytosis of peritoneal macrophages were measured. The levels of interleukin-2 （IL-2）, interferon-γ （IFN-γ）, tumor necrosis factor-α（TNF-α） in serums and activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px）, and the contents of malondialdehyde （MDA） in livers were measured by using commercial reagent kits. The results showed that black tea polyphenols significantly inhibited H22 hepatoma cells growth in mice, the tumor inhibition rate was 46.04% in the low-dose group [250 mg/（kg·d）] and 63.32% in the high-dose group [500 mg/(kg·d）] at the end of the experimental period. Compared with the model group, black tea polyphenols could significantly promote splenocyte proliferation, killing activity of NK cells, and macrophage phagocytosis（P<0.05）. In addition, the ratio of T cells in peripheral blood, the levels of IL-2, IFN-γ, TNF-α in serum and the activities of SOD, GSH-Px in liver were significantly increased （P<0.05) in the high-dose group, while MDA levels were significantly reduced （P<0.05）. In conclusion, the black tea polyphenols exhibit a strong antitumor activity in vivo. The underlying mechanism might be related to enhancing antitumor immune response and improving antioxidant function in the body.