Nanoscale coordination polymers (NCPs) self-assembled from metal ions and organic bridging ligands exhibit many unique features promising for applications in nanomedicine. In this work, manganese dioxide (MnO₂) nanoparticles stabilized by bovine serum albumin are encapsulated byNCP-shells constructed based on high-Z element hafnium (Hf) ions and c,c,t-(diamminedichlorodisuccinato)Pt(IV) (DSP), a cisplatin prodrug. After furthermodification with polyethylene glycol (PEG), the formed BM@NCP(DSP)-PEG can simultaneously serve as a radio-sensitizer owing to the strong X-ray attenuation capability of Hf to enhance radiotherapy, as well as a chemotherapeuticagent resulting from the reduction-induced release of cisplatin. Meanwhile, the in situ generated oxygen resulting from MnO₂-triggereddecomposition of tumor endogenous H₂O₂ will be greatly helpful for overcominghypoxia-associated radio-resistance. Upon intravenous injection, BM@NCP(DSP)-PEG shows efficient tumor homing as well as rapid renalexcretion, as illustrated by magnetic resonance imaging and confirmed by biodistribution measurement. Notably, an excellent in vivo tumor growthinhibition effect is observed with BM@NCP(DSP)-PEG nanoparticles after the combined chemoradiotherapy treatment. Therefore, the NCP-based compositenanoparticles with inherent biodegradability and no appreciable in vivotoxicity may be a unique type of multifunctional nanoplatform responsive to different parameters in the tumor microenvironment, promising for cancer theranostics with great efficacy.