Apoptosis　has　gained　increasing　attention　in　cancer　therapy　as　an　intrinsic　signaling　pathway,　which　leads　to　minimal　leakage　of　waste　products　from　a　dying　cell　to　neighboring　normal　cells.　Among　various　stimuli　to　trigger　apoptosis,　mild　hyperthermia　is　attractive　but　confronts　limitations　of　non-specific　heating　and　acquired　resistance　from　elevated　expression　of　heat　shock　proteins.　Here,　a　dual-stimulation　activated　turn-on　T1　imaging-based　nanoparticulate　system　(DAS)　is　developed　for　mild　photothermia　(≈43 °C)-mediated　precise　apoptotic　cancer　therapy.　In　the　DAS,　a　superparamagnetic　quencher　(ferroferric　oxide　nanoparticles,　Fe3O4　NPs)　and　a　paramagnetic　enhancer　(Gd-DOTA　complexes)　are　connected　via　the　N6-methyladenine　(m6A)-caged,　Zn2+-dependent　DNAzyme　molecular　device.　The　substrate　strand　of　the　DNAzyme　contains　one　segment　of　Gd-DOTA　complex-labeled　sequence　and　another　one　of　HSP70　antisense　oligonucleotide.　When　the　DAS　is　taken　up　by　cancer　cells,　overexpressed　fat　mass　and　obesity-associated　protein　(FTO)　specifically　demethylates　the　m6A　group,　thereby　activating　DNAzymes　to　cleave　the　substrate　strand　and　simultaneously　releasing　Gd-DOTA　complex-labeled　oligonucleotides.　The　restored　T1　signal　from　the　liberated　Gd-DOTA　complexes　lights　up　the　tumor　to　guide　the　location　and　time　of　deploying　808 nm　laser　irradiation.　Afterward,　locally　generated　mild　photothermia　works　in　concert　with　HSP70　antisense　oligonucleotides　to　promote　apoptosis　of　tumor　cells.　This　highly　integrated　design　provides　an　alternative　strategy　for　mild　hyperthermia-mediated　precise　apoptotic　cancer　therapy.　©　2023　Wiley-VCH　GmbH.