In this study, we discovered that hepatocyte growth factor (HGF), a cytokine highly expressed by bone marrow mesenchymal stem cells within the microenvironment, activates the AKT, ERK and STAT3 signaling pathways, promotes the expression of anti-apoptotic proteins BCL-2, MCL-1, and BCL-xL, thereby enhancing CLL cell survival and resistance to both natural and ABT-199-induced apoptosis. Here, STAT3 is linked to B-cell chronic lymphocytic leukemia.