Mild　photothermal　therapy　(mPTT)　has　emerged　as　a　highly　promising　approach　for　tumor　ablation.　However,　the　heat-induced　overexpression　of　heat　shock　proteins　(HSPs)　limits　its　efficacy　by　increasing　cellular　temperature　tolerance.　Herein,　a　self-catalytically　enhanced　mild　PTT　strategy　that　directly　disrupts　the　structure　of　HSPs　to　restore　tumor　cell　sensitivity　is　proposed.　In　the　proof-of-concept　study,　AgFeCu　nanoparticles　(AgFeCu　NPs)　with　dual-active　catalytic　centers　(Fe-Cu)　and　near-infrared　photothermal　properties　are　developed.　The　AgFeCu　NPs　can　efficiently　catalyze　the　conversion　of　endogenous　hydrogen　peroxide　into　hydroxyl　radicals　in　situ,　leading　to　the　degradation　of　HSPs　and　enhancing　the　therapeutic　effects　of　mild　PTT　mediated　by　their　Ag-based　substrates.　Furthermore,　AgFeCu　NPs　can　also　induce　oxidative　stress　by　depleting　intracellular　glutathione　and　promoting　lipid　peroxidation,　thereby　triggering　tumor　ferroptosis　and　resulting　in　significant　tumor　elimination　in　a　U87MG　murine　tumor　model.　This　self-catalytically　enhanced　strategy　maximizes　the　efficacy　of　mild　PTT　while　minimizing　damage　to　healthy　tissues,　which　is　expected　to　provide　valuable　insights　for　the　development　of　next-generation　photothermal　nanoagents　for　improved　tumor　therapeutics.