Objective To analyze whether human-derived ICOSIg can bind specifically to ICOSL on mouse immature dendritic cells(DCs) and to explore its biological functions. Methods The binding of ICOSIg to immature DCs was observed by FCM. The cytotoxic effect of ICOSIg on DCs was examined by Annexin Ⅴ/PI, CFSE staining, and CCK-8 kit. thymine incorporation was used to analyze the blocking effect ICOSIg on mixed lymphocyte reaction (MLR). Results Human-derived soluble fusion protein ICOSIg could bind to ICOSL on mouse bone marrow-derived immature DCs and inhibited the MLR, but it neither induced early or late apoptosis of DCs nor affected their proliferation. Conclusion Human-derived ICOSIg constructed in this study has a potent biological function; it has no toxic effect against mouse immature DCs. It is demonstrated that human-derived ICOSIg can sepecifically bind to ICOSL on mouse immature DCs.