Zein and its complexes have been considered as promising carriers for encapsulating and delivering various biological active ingredients, however, there still have some issues about Zein-based drug delivery systems should be considered, including poor colloidal stability, low drug encapsulation efficiency as well as rapid initial drug release, and uncontrollable release. In this work, we reported for the first time that hyperbranched polymers (HPG) functionalized Zein with terminal alkyne (Zein-HPG-PA) can be used for loading anticancer agent curcumin (CUR) via a facile phenol-yne click reaction. The resultant product (Zein-HPG-PA@CUR) displays high drug loading capacity, small particle size and excellent water dispersibility. More importantly, almost no CUR was released from Zein-HPG-PA@CUR under pH 7.4 and the cargo will be gradually released under acidic environment. As compared with free CUR, Zein-HPG-PA@CUR shows considerable cytotoxicity towards MDA-MB-231 cells under dark environment, while the cytotoxicity was significantly enhanced upon light-irradiation, implying great potential of Zein-HPG-PA@CUR for cancer treatment. Considered the above aspects, we believe that this work should be of significant impact on the biomedical applications of Zein, especially for fabrication of Zein-based responsive drug delivery systems.