Abstract: Mesenchymal stem cells (MSCs) have a strong secretory capacity. Many studies have shown that the functions of MSCs are mainly mediated through the secretion of various cytokines and extracellular vesicles (EVs). Additionally, exosomes represent the main subpopulations of EVs. As important components of the intracellular signaling of MSCs, MSC-derived exosome (MSC-Exo) has similar effects as MSCs on hepatocellular carcinoma (HCC) and other diseases. Exosomes can overcome complex delivery barriers in vivo to achieve longdistance transportation, and they can be absorbed by recipient cells without immune rejection and tumorigenicity. Moreover, exosomes are easily available and can be conveniently stored. The lipid membrane of MSC-Exos can wrap around and protect its contents from the activity of degrading enzymes in the receptor fluid, making them good natural carriers for anti-hepatocellular carcinoma drugs. Therefore, MSC-Exos possess great clinical application prospects in the stem cell-based treatment of HCC. This article briefly reviews the progress on MSC-Exo in the treatment of HCC and provides new ideas for future research.