A supramolecular assembly was successfully constructed from tetraphenylethylene-bridged β-cyclodextrin tetramers (TPECD) and adamantyl-grafted hyaluronic acids (HAAD) and fully characterized by UV-vis spectroscopy, fluorescence emission spectroscopy, zeta potential, SEM, AFM and TEM. The obtained TPECD–HAAD assembly, which existed as spherical nanoparticles with an average diameter of 50 nm, emitted stronger fluorescence than free TPECD due to the restricted intramolecular rotation. Significantly, this supramolecular assembly can efficiently load the anticancer drug doxorubicin (DOX) into cancer cells, and the resultant DOX@TPECD–HAAD system had higher anticancer ability and fewer side effects than free DOX.