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Hyaluronic acid (HA) is a nonsulfated glycosaminoglycan and a major component of the extracellular matrix. HA is overexpressed by numerous tumor cells, especially tumor-initiating cells. HA-based nanomaterials play in importance role in drug delivery systems. HA is used in various types of nanomaterials including micelle, polymersome, hydrogel, and inorganic nanoparticle formulations. Many experiments show that HA-based nanomaterials can serve as a platform for targeted chemotherapy, gene therapy, immunotherapy, and combination therapy with good potential for future biomedical applications in cancer treatment.