Hyaluronic acid (HA) is being actively studied as a drug carrier due to its favorable properties and functional groups for chemical modification. Despite its high functionality, pKa of HA (3-4, carboxyl groups) is inappropriate to release the drugs at the tumor pH. For the development of a pH-sensitive nanocarrier based on HA for anticancer drugs, HA-graft-imidazole-dodecylamine (HID) was synthesized. The HID formed a stable nanocarrier with ca. 151 nm size and low critical association concentration (CAC) at pH 7.4 and was destabilized in acidic conditions (pH 6.8- 6.0) with increased size and CAC. Doxorubicin loaded HID nanocarriers (DHNs) exhibited pH-dependent drug release with the structural change by the deprotonation and protonation of the imidazole groups in HID. The low CAC of HID at physiological pH and the pH-dependent drug release would confer high stability and prevent drug loss during systemic circulation. It might reduce the toxicity to normal tissue at physiological pH. In addition, tumor extracellular pH and early endosomal pH environments triggered the disintegration of nanocarriers, switching the drug release higher than in other normal tissues and blood. Consequently, HID could be a biocompatible pH-sensitive drug carrier for cancer chemotherapy.