Mesenchymal stem cells (MSCs), which have the potential of self-replication and differentiation, are a very valuable cell source for stem cell-based medical therapy. Their application has opened up a new way for diseaseresearch. Although MSCs can maintain cell stemness through self-renewal, with the prolongation of cell passage and culturetime, the stemness of MSCs gradually decays, and the cell aging and differentiation potential decreases gradually. Autophagy is a highly conserved cytological process that degrades the modified, excess, and deleterious cytoplasmic components in autophagosomes, which are then degraded by fusion with lysosomes. As the main intracellular degradation and recycling pathway, autophagyplays an active role in maintaining cellhomeostasis, self-renewal and pluripotency. In this paper, the role of autophagy in self-renewal and maintenance of multidirectional differentiation potential of MSCs was reviewed, which laid a theoretical foundation and practical basis for the research and application of MSCs.