Hyaluronic acid (HA) is a relatively new polymer for the construction of drug delivery systems. CD44 and the receptor for HA-mediated motility play a key role in vivo for the receptor-mediated endocytosis of HA. Cellular uptake and the efficiency of tumor-targeted drug delivery are supposed to increase through utilizing HA as drug carriers. Currently, HA has provided a promising platform to physically encapsulate or chemically conjugate with various drugs. In this review, we presented the most latest advances in HA-based drug delivery systems and some forward-looking ideas are discussed.