Metal–organic frameworks (MOFs), a class of materials consisting of metal ions with organic ligands, exhibit many enviable properties including good biocompatibility, rich chemical diversity, and high surface area.[10] Nanoscale MOFs have been widely used in drug delivery, photodynamic therapy, and radiation therapy for cancer.[11] Herein, we constructed MnO2‐modified zeolitic imidazolate framework‐8 (ZIF‐8, a kind of Zn2+ based MOF) nanoparticles to degrade mutp53 and activate the cGAS‐STING pathway for enhanced immunotherapy. The gene discussed is CGAS; the disease is cancer.