Current studies have found that allogenic mesenchymal stem cells (MSCs) transplantation (MSCT) can be used successfully in mouse and human SLE. However, syngeneic bone marrow (BM)-MSCT was ineffective. Recently, studies also revealed that BM-MSCs from SLE patients showed senescent behavior. These findings suggested that the senescence of BM-MSCs from SLE patients may be a contributing factor to disease pathogenesis. So further findings about MSCs senescence of SLE will contribute to lay the groundwork for the development of new therapeutic approaches to treat SLE. In this review, we summarize the characteristics of MSCs, molecular mechanisms and signaling involved in MSCs senescence and the senescent biological behavior of MSCs from SLE and possible mechanisms. Analyzing the mechanisms of controlling MSCs senescence may provide a therapeutic target for SLE.