The objective is to study the effect of zymosan on antioxidant and immune function of S180 tumor-bearing mice. Seventy Kunming mice were randomly divided into seven groups: a normal control group (NC), a tumor control group (TC), three dose groups of zymosan (low, medium, high), a cyclophosphamide (Cy) group, and a combination of zymosan and Cy group. The S180 tumor-bearing mice model was established by the inoculation of cancer cell suspension subcutaneously in the mouse’s right anterior limb. At the 19th day, malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activity in liver homogenate were analyzed. The reverse transcriptase-polymerase chain reaction was used to determine the mRNA expression levels of IL-2, TNF-α, and TGF-β1. The activity of GSH-Px and SOD in the liver increased with the dose of zymosan, whereas the activity of MDA significantly decreased in the higher-dose groups of zymosan, compared to the TC group (P < 0.01). In the zymosan groups, mRNA expression levels in tissues of S180 tumor-bearing mice were significantly higher for TNF-α and IL-2, but lower for TGFβ1 than in the Cy or TC group (P < 0.01). The high-dose of zymosan markedly showed a depressant effect on S180 tumor, enhanced by the action of Cy that increased mRNA expression levels of TNF-α and IL-2. The mechanism of zymosan on the inhibition of tumor growth may be due to its ability to enhance the antioxidant and immune function in a dose-dependent manner.