Myelodysplastic syndromes (MDS) comprise a group of malignant hematopoietic stem cell (HSC) disorders characterized by ineffective hematopoiesis. The risk of transformation to acute myeloid leukemia (AML) is increasing. The initiating event in HSC of MDS leads to a growth advantage and subsequent clonal expansion, that is still poorly understood. Accumulating data indicate that the mesenchymal stem cells(MSCs) in MDS model display aberrant characteristics contributing to disease initiation and transformation into AML. MSC derived from MDS displayed the alteration in genetics, epigenetics and gene expression, which contribute to altered morphology, impaired proliferative and differentiation capacity and perturbed cytokine secretions, thus destroy in their ability to support normal hematopoiesis and contribute to malignant progression. A number of promising agents that target the interactions of the MDS clone with MSC are currently investigated in various phases of clinical trial, that might ultimately result in novel therapeutic strategies, targeting niche cells to attenuate leukemic progression. In this article, the current status of MDS treatment, the characteristics of MDS-MSC senescence and phenotypes, the changes of hematopoietic function sapported by senescent MDS-MSC, the significane of MDS-MSC in MDS prognosis and the MDS-MSC as potential target for treatment of MDS are summarized.