ABSTRACT In this paper, Biocompatible supramolecular hydrogels, composed of β-cyclodextrin-modified hyaluronic acid, pluronic F127, α-cyclodextrin and doxorubicin, were constructed, which can be employed for targeted delivery system. The chemical composition and rheological properties of the obtained hydrogels were fully characterised. Considering the controlled complexation between DOX and the hydrogel skeletons, the controlled release of hydrogel G[5, 10, 5] was investigated to exhibit a better pH- and temperature-controlled release behavior. The data of DOX release kinetic was fitted well with Higuchi and Korsmeyer-Peppas models. Moreover, the cellular toxicity experiments indicated that the hydrogel DOX@G[5, 10, 5] exhibited a similar anticancer ability in comparison with free DOX. Due to the hyaluronic acid-targeted effects, the cytotoxicity of the hydrogel DOX@G[5,10,5] to HepG2 cells was lower than that to SKOV-3 cells upon increasing the concentration. Therefore, these hydrogels may act as a potential prospect for the targeting release of anticancer drugs.