Mesenchymal stem cells (MSCs) have the ability of self-renewal and differentiation into multiple tissues. The senescence of MSCs may involve some age related disease and autoimmune disease such as SLE. Senescent MSCs may limit MSCs clinical application. Thus, analysis of in vitro senescence in MSC is crucial for quality control of MSCs preparations used for therapeutic application. This review summarizes recent advances about main characteristics of senescent MSCs, molecular mechanisms and signal pathway of MSCs senescence.