Mesenchymal stem cells (MSC) have attracted high attention to their various origins, capability of multi-lineage differentiation, supporting hematopoiesis and regulating immunity. Consequently, MSC show great potential for tissue engineering and cell/gene therapy. The bone marrow microenvironment plays an important role in the pathogenesis of several hematological malignancies. It was confirmed that as key components of the hematopoietic microenvironment, MSC correlated complexly with tumor microenvironment. Recent reports showed that MSC from some patients with AML, MDS, ALL and MM harboured cytogenetic alterations. In addition, the phenotype, ability of differentiation and immunoregulatory function of MSC displayed different degree of abnormalities, suggesting that MSC played a role in the pathophysiological mechanism of malignant hematopoietic diseases. Besides, MSC have been found to participate in drug resistance of antileukemic therapy. Hematopoietic stem cell transplantation (HSCT) has become an important treatment approach for the malignant hematopoietic diseases in recent years. Because of the advantages of supporting hematopoiesis and regulating immunity, MSC are used to promote the engraftment and prophylaxis/treatment of GVHD. This review summarized briefly the abnormalities of mesenchymal stem cells in malignant hematological diseases and MSC research advances on cell therapy.