The real-time tracking and efficacy evaluation of therapeutic nanoplatforms especially in deep-tissues is of great importance but faces challenges. Meanwhile, chemodynamic therapy (CDT), relying on Fenton reaction by converting H 2 O 2 into toxic hydroxyl radicals (•OH), has drawn wide interests in the fabrication of nanozymes for tumor therapy, while endogenous H 2 O 2 is usually insufficient for effective CDT. Here, we report the pH-responsive multifunctional nanoplatforms consisting of copper peroxide (CP) nanoparticles, paclitaxel (PTX) and perfluoro-15-crown-5-ether (PFCE), for 19 F magnetic resonance imaging guided and enhanced chemo-chemodynamic synergetic therapy with self-supplied H 2 O 2 stemmed from the decomposition of CP nanoparticles under acid conditions in tumor. The decomposition of CP nanoparticles further promotes the release of PTX for enhanced chemotherapy. Both in vitro and in vivo results indicate that the efficient generation of •OH and drug release effectively inhibits tumor growth. Furthermore, 19 F MRI signal can clearly track the fate of nanoplatforms in tumor and guide tumor treatment. This work provides a promising strategy for the rational design and construction of multifunctional nanoplatforms for imaging-guided synergistic therapy of deep seated tumor.