This study was carried out to evaluate the effects of a Huaier polysaccharide (TP-1) on the tumor growth and immune function in hepatocellular carcinoma (HCC) H22-based mouse in vivo. Results showed that TP-1 was capable of repressing transplanted H22 solid hepatic tumor cell growth in vivo, prolonging the live time of mice bearing ascetic H22 tumors, and repressing the pulmonary metastasis of H22-bearing mice. Moreover, the relative weight of immune organ (spleen and thymus) and lymphocyte proliferation were improved after TP-1 treatment. Furthermore, the treatment with TP-1 could promote immune-stimulating serum cytokines, such as IL-2 and IFN-γ, but inhibit immune-suppressing serum cytokines IL-10 secretion in H22-bearing mice. Besides, the percentage of CD4+ T cells and NK cells was increased, whereas the number of CD8+ T cells decreased in tumor-bearing mice following TP-1 administration. In addition, this compound displayed little toxic effects to major organ of tumor-bearing mice at the therapeutic dose, such as the liver and kidney. This experimental finding suggested that TP-1 exhibited prominent antitumor activities in vivo via enhancement of host immune system function in H22 tumor-bearing mice. This product could be developed individually as a safe and potent biological response modifier for HCC therapy.