Gene editing is to insert, delete, modify or replace target gene into the genome of a living organism. The most common technique is to import a recombinant vector (such as a plasmid or lentivirus containing a target-gene) in order to get one new hereditary mark to change the target cells’ function and characteristics or differentiate target cells into a particular direction. Mesenchymal stem cell (MSC) is a kind of pluripotent stem cells with high ability of self-proliferation and can be differentiated into osteoblasts, chondrocytes, adipocytes, etc. Because of its potential of multidirectional differentiation, with the development of regenerative medicine, MSC has become one of the ideal seeding cells for tissue engineering and cell therapy. Researches have shown that gene editing technique regulates the differentiation of MSCs. In this review, we mainly discuss the latest research progress in gene editing techniques applied in mesenchymal stem cells’ differentiation.