Abstract: Human serum albumin (HSA) is a natural transport protein in the blood. Its physiological function is mainly to combine with various endogenous substances and exogenous molecules, and then to transport them to various tissues in the body. The internal binding sites and surface-active groups of HSA enable it to carry multiple molecules simultaneously for multifunctional therapy. In addition, under mild conditions, HSA can also be used to prepare drug-loaded nanoparticles via different methods. HSA-based drug delivery systems have received increasing attention in recent years due to their biodegradability, non-immunogenicity, biocompatibility, and long half-life. This article reviews the latest research progress of HSA-based drug delivery systems, and presents the challenges and future development directions for the clinical translation of HSA preparations.