Abstract: Skin injury is the breakdown of the epidermis, mucous membranes, or tissue due to disease or external violence. Mesenchymal stem cells (MSCs) to repair skin damage have become an option to accelerate skin wound healing. In addition to their differentiation into skin resident cells, the mechanism of wound healing induced by MSCs is mainly contributed to their paracrine effect. As the main component of paracrine, exosomes lay the foundation for the realization of “cell-free therapy”. In recent years, exosome-based tissue regeneration therapeutics are being extensively studied, but the specific mechanisms of exosome in promoting skin healing and methods for in vivo applications are still being refined. This article will review the mechanism and application of mesenchymal stem cell-derived exosomes in skin wound repair.