Tumor　hypoxia　and　the　tissue　penetration　limitation　of　excitation　light　hamper　the　widespread　clinical　use　of　photodynamic　therapy.　The　development　of　new　therapeutic　strategies　that　can　generate　oxygen-independent　free　radicals　without　penetration　depth　limitation　is　of　great　demand.　Herein,　a　novel　magnetothermodynamic　strategy　for　deep-seated　tumor　therapy　is　reported.　In　this　system,　a　radical　initiator　(AIPH)　was　loaded　into　porous　hollow　iron　oxide　nanoparticles　(PHIONs).　Under　the　induction　of　an　alternating　magnetic　field　(AMF),　PHIONs　can　generate　heat　to　trigger　the　release　and　decomposition　of　AIPH,　resulting　in　the　generation　of　oxygen-independent　alkyl　radicals.　The　resulting　alkyl　radicals　can　effectively　kill　cancer　cells　under　hypoxic　conditions.　More　importantly,　this　magnetothermally　triggered　free-radical　generator　exhibits　significant　therapeutic　efficacy　for　orthotopic　liver　tumors　in　a　rat　model.　This　magnetothermodynamic　therapy　strategy　with　the　advantages　of　oxygen　independence　and　no　limitation　of　penetration　depth　holds　great　promise　in　deep-seated　solid　tumor　treatment.　©　2021　American　Chemical　Society.