The appearance of drug-resistant (especially, multidrug-resistant (MDR)) tumor cells is a major obstacle to the success of chemotherapy; thus, the development of effective anti-MDR agents plays an important role in the tumor therapy. In this report, the considerable effect of nano-TiO2 and UV illumination on the drug resistance of target cancer cells has been explored, and the fresh evidence from the fluorescence spectroscopy and microscopy as well as electrochemical studies demonstrates the significant enhancement effect of nano-TiO2 to the drug uptake by drug-resistant leukemia cells. Besides, it is also observed that the combination of the nano-TiO2 and UV irradiation with the accompanying anticancer drug daunorubicin could provoke some considerable changes of the cell membrane of the target leukemia cells, which indicates that nano-TiO2 could not only increase the drug accumulation in target cancer cells, but also act as an effective anti-MDR agent to inhibit the relative drug resistance.