A microwave thermal therapy was proposed based on the strategy of microwave sensitizers and the susceptibility of the tumor tissue for enhancing thermal antitumor therapy. Display omitted Although surgical resection and chemotherapy were widely applied in tumor therapy, the dysfunction of normal cells resulted in the side effects (such as anorexia, nausea). MW thermal therapy is a non-invasive anticancer strategy under the help of MW sensitizer, with the safety and higher efficacy. Zirconium metal-organic framework nanocubes (ZrMOF NCs) modified with polyethylene glycol, were prepared via one pot method and carbodiimide technique, resulting in their large specific surface area and porosity. Our results showed that non-ion-loaded ZrMOF NCs in 0.9% NaCl solution exhibited better heating effect, higher than that in pure water, due to the robust collision among the ions under MW irradiation. The in vivo experiments confirmed that ZrMOF-PEG NCs+MW group exhibited the higher temperature in the tumor region than that of only MW treatment, suggesting a better MW thermal therapeutic anticancer efficacy. This work provides a new preparation strategy of biosafety nanomaterial as MW sensitizer for enhancing MW thermal anticancer therapy.