As the progenitor of most cell components in the hematopoietic microenvironment, mesenchymal stem cells (MSC) exhibit self-renewal and multilineage differentiation capacity. Through direct interaction with hematopoietic cells, secreting extracellular matrix and factors, MSC maintain the integrity of hematopoietic microenvironment and regulate hematopoiesis accurately. This review summarized the function of MSC in hematopoietic regulation, such as secretion of cytokines supporting hematopoiesis, MSC expression and adhesion molecules interacting with hematopoietic cells, and supportive effects of transplantation combining MSC with HSC on hematopoietic reconstruction, and its clinical perspectives.