Objective To investigate the effect of guanylate-binding protein 2 (GBP2) on β-glucan-induced maturation and immune response of dendritic cells (DCs). Methods RNA-microarray and real time quantitative PCR were used to investigate the change of genes in DCs induced by β-glucan. Thereafter, DCs were transfected with GBP2 siRNA to knock down the expression of GBP2. Flow cytometry was used to detect the surface markers (CD11c, MHC-II, CD80) on DCs as well as the proliferation of T cells. Cytokines (IL-6, IL-12p70, TNF-α, IL-10) were tested by ELISA. Results The expressions of DC surface markers, including CD11c, MHC- II, CD80, were significantly down-regulated after the cells were transfected with GBP2 siRNA. Moreover, the production of IL-6, IL-12 and TNF-α were also depressed. OVA specific T-cell proliferation decreased when OT-II T cells were co-cultured with GBP2-siRNA transfected-DCs. Conclusion GBP2 can effectively regulate β-glucan-induced maturation of DCs, thus suppressing the proliferation of T cells.