Cytotoxic T lymphocytes (CTLs) exert cytotoxicity against tumor cells with granzyme B and porforin (two important components for cytotoxicity). One main reason for the limitation of clinical success in tumor immunotherapy is tumor cell inefficacy in inducing sufficient immune responses, such as efficient CTLs, and subsequently sufficient granzyme B and porforin activity because of weak immunogenicity of the tumor cells. It is therefore important to boost tumor cells to induce efficient CTLs and sufficient granzyme B and porforin. We suggest that Ganoderma lucidum polysaccharides (Gl-PS), with multiple bioactivities have this potential. We have shown that after incubation with Gl-PS, B16F10 melanoma cells, which are deficient in antigen presentation, promoted cytotoxicity of CTLs against B16F10 cells, induced more granzyme B and porforin in CTLs, decreased the in vivo incidence of tumorigenesis 15 days after inoculation and prolonged the latency of tumorigenesis 21 days after inoculation, demonstrating that the effects of Gl-PS on B16F10 cells induced stronger immune responses against tumor cells.