This paper applied mesoporous metal-organic frameworks (MOFs) of UiO-66 particles for pH-responsive doxorubicin (DOX) delivery and cancer treatment. Mesoporous structured UiO-66 MOFs were synthesized, and carboxymethylcellulose (CMC) was loaded for sensitive pH response and also as a linker to encapsulate the chemotherapeutic drug of DOX. The composite of UiO-66/CMC@DOX was synthesized, and the loading capacity was as high as 45 μg DOX per mg of the carrier. The structure and crystalization of the UiO-66 MOFs were determined by the Transmitting Electron Microscope (TEM) and x-ray diffraction methods, while the loading of CMC and DOX was inspected by Fourier Transform InfraRed (FT-IR) and UV–vis spectroscopy. The DOX release from UiO-66/CMC@DOX was tested under different pH at 37 °C. The DOX accumulative release could reach 78% under the pH of 5. A lower pH was more favorable for DOX release due to the CMC shrinking and higher DOX solubility in an acidic environment. The cytotoxicity study indicated that, under the DOX concentration of 4 μg ml−1, the A549 cell (Lung Carcinoma Cell Line) viability of UiO-66/CMC was 28%, which was lower than that from free DOX solution (47%). UiO-66 MOFs were demonstrated to be an efficient drug delivery carrier for chemotherapeutic drug and release.