Context: Grifola frondosa (Polyporaceae), maitake, is a widely consumed edible mushroom in some Asian countries. The fruit bodies and mycelia of maitake have shown different bioactive compounds with anticancer and other therapeutic properties. Objective: This study evaluated three chemically modified maitake polysaccharide-peptides' (MPSP) adjuvant effect (in vivo) and anticancer activity (in vitro growth inhibitory effect) compared with crude MPSP from G. frondosa. Materials and methods: We investigated the possibility of enhancing the adjuvant effect and anticancer effect of crude MPSP by using simple chemical modification methods to convert crude MPSP to phosphorylated, acetylated or esterified MPSPs. The adjuvant effect and growth inhibitory effect were evaluated by C6 cell inoculated rat model with cyclophosphamide (CPA) treatment and in vitro cell viability assay, respectively. Results: All four tested MPSPs showed significant adjuvant effect to CPA treatment on rats inoculated with C6 cancer cells. In addition, an obvious growth inhibitory effect was observed in C6 cancer cells but not in normal brain cells treated with various forms of MPSPs. Only phosphorylation could significantly (p esterified MPSP ≥ acetylated MPSP ≥ crude MPSP) of efficacy was observed in both the in vivo and in vitro assays. Discussion and conclusion: This study showed chemical phosphorylation could markedly enhance both adjuvant effects and growth inhibitory effects. This study demonstrated the feasibility of enhancing the efficacy of MPSP by using a simple chemical modification method, and this provides a foundation for future study in this area. ; Department of Applied Biology and Chemical Technology