Abstract: Deoxycholic acid-1-(triphenylmethyl)-L-histidineDOCA-His(Trt) was synthesized by amidation of deoxycholic acid (DOCA) with 1-(triphenylmethyl)-L-histidine methyl ester monohydrochloride (H-His(Trt)-OMe·HCl). HA-DOCA-His(Trt)was synthesized by grafting the carboxyl group of hyaluronic acid(HA) with an amine group of DOCA-His(Trt) in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). HA-DOCA-His was obtained by deprotection of Trt group from HA-DOCA-His(Trt). FT-IR was used to confirm the chemical structure of HA-DOCA-His. Results showed that the hemolysis of HA-DOCA-His micelles was significantly lower than that of Tween 80, and was comparable to that of Cremophor EL. Paclitaxel (PTX) loaded HA-DOCA-His micelles were prepared by ultrasonication method. Dynamic dialysis method was employed to study the PTX release from HA-DOCA-His micelles, which showed a pH-dependent release manner. In vitro cytotoxicity exhibited HA-DOCA-His micelles performed stronger cell proliferation inhibition efficacy than PTX solution. HA-DOCA-His polymeric micellar system with CD44 receptor targeting and endosome pH sensitivity, could provide an effective approach for targeting intracellular delivery and endosome drug release of anticancer drugs.