In this study, cross-linked hyaluronan-styrylpyridinium (HA-SbQ) micelles were prepared to be used as a novel carrier for paclitaxel (PTX). PTX was successfully encapsulated into the hydrophobic cores of the cross-linked micelles using the dialysis method. The resultant PTX-loaded cross-linked HA-SbQ micelles were about 113 nm in diameter with spherical shape and high encapsulation efficiency. Fluorescence microscopy and high-performance liquid chromatography studies showed that PTX-loaded cross-linked HA-SbQ micelles had excellent cellular uptake ability by bone marrow derived macrophages (BMM) and human glioma U87 cells. Cellular uptake of cross-linked HA-SbQ micelles was found to be higher than that of un-cross-linked ones due to smaller size and more stable structure. In vitro cytotoxicity studies also revealed that the PTX-loaded cross-linked micelles were more potent than those of PTX-loaded un-cross-linked micelles and free PTX. These results suggested that cross-linked HA-SbQ micelles could be a potential vehicle for delivering hydrophobic chemotherapeutic drugs to tumors.