Although　photothermal　therapy　(PTT)　has　become　a　compelling　strategy　for　cancer　therapy,　few　studies　concern　the　physiological　consequences　of　PTT　ablation.　Herein,　we　discover　that　PTT-induced　hyperthermia　can　aggravate　tumor　hypoxia,　which　may　increase　the　risk　of　tumor　recurrence　and　reduce　PTT　efficacy.　We　thus　integrated　the　pH/hypoxia-triggered　Fe(iii)-banoxantrone　(AQ4N)　prodrug　and　semiconducting　polymer　dots　(SPs)　for　programmable　triggered　cancer　photothermal-chemotherapy.　A　SP-hybridized　mesoporous　silica　framework,　decorated　by　dopamine　and　polyethylene　glycol,　named　PPMSF,　was　synthesized　by　a　simple　method,　and　then　served　as　an　efficient　photo-absorbing　agent　(PTA)　and　drug　carrier.　Fe(iii)-AQ4N　and　Mn(ii)　were　then　coordinated　with　PPMSF　(abbreviated　Mn-APPMSF)　via　coordination　effects.　The　nanohybrids　exhibited　tumor　micro-environment　pH　triggered　drug　release.　Under　the　irradiation　of　NIR　light,　magnetic　resonance　imaging　(MRI)　tracked　the　accumulation　of　the　nanohybrids　in　tumors　which　then　destroyed　tumor　cells　by　local　hyperthermia,　this　can　consequently　aggravate　the　tumor　hypoxia　levels.　Intriguingly,　the　aggravated　hypoxia　can　further　enhance　the　reduction　of　AQ4N　to　significantly　improve　therapeutic　efficacy　and　effectively　inhibit　tumor　growth　when　compared　with　traditional　PTT.　These　results　indicate　the　potential　of　our　nanohybrids　as　a　programmable　synergistic　agent　for　cancer　therapy.　©　The　Royal　Society　of　Chemistry　2018.