Mesenchymal stem cells (MSCs) possess the ability to self-renew and give rise to highly differentiated cell types, and can be isolated from a wide range of sources, making them the first choice for cell therapy. MSCs are widely used in tissue repair, autoimmune diseases and degenerative diseases, and have high value. Currently, biosafety is one of the most challenging problems in the clinical translation of MSCs. Previous research on the biosafety of MSCs has been largely unclear. Therefore, we reviewed the research progress on several aspects of MSC biosafety, including genetic stability, tumorigenicity and immunogenicity. This review may provide a reference for the safety evaluation and clinical transformation of MSCs.