Abstract: Azurin is a copper protein and possesses antitumor activity. The H117G mutant of Azurin (Az-H117G) was prepared, which is capable to bind exogenous imidazole or histidine. The interaction of Az-H117G with imidazole-based derivatives was investigated using UV-vis spectroscopy. Results show that the protein mutant can bind imidazole, histidine and Pt-His complex, a Pt(IV) prodrug of cisplatin. Based on this information, the protein/drug conjugate was prepared and the anti-proliferation of tumor cells was studied. The result indicates that this protein/drug conjugate might be potentially applicable to antitumor drug design.