As a member of the B7 family, inducible co-stimulator ligand (ICOSLG) expressed on tumor cell has been reported to have an important role in tumor immunity. In this study, we sought to determine whether the expression of ICOSLG in mouse hematological malignancy cells influences GVL reaction after mouse allogeneic BMT. In our study, we analyzed the expression of ICOSLG in six mice hematological malignancy cell lines for the first time, and found that FBL3, A20 and P388 cells expressed high levels of ICOSLG. Then, we chose A20 cells as targets to construct a GVL model and study the effects on the GVL reaction by silencing the ICOSLG gene. The survival was analyzed. We found that in GVL model, mortality of interference groups was significantly delayed compared with the control group (P = 0.0005). Our results indicate that knockdown of ICOSLG of mouse leukemic cells may significantly enhance GVL effect after allogeneic BMT.