Owing　to　its　aggressive　biological　behavior,　the　lack　of　specific　targets,　and　the　strong　therapeutic　resistance　of　triple　negative　breast　cancer　(TNBC),　current　therapeutic　strategies　are　still　limited.　The　combination　of　multiple　treatments　has　been　confirmed　as　a　promising　strategy　for　TNBC　therapy.　However,　the　efficacy　of　combination　therapy　can　be　restricted　due　to　increasing　therapeutic　resistance　to　various　treatments.　Herein,　we　constructed　a　nanodiamond　(ND)-based　nanoplatform　for　augmented　mild-temperature　photothermal/chemo　combination　therapy　against　TNBC,　weakening　the　therapeutic　resistance　via　autophagy　inhibition　enabled　by　the　NDs.　A　layer-by-layer　self-assembly　approach　was　utilized　to　construct　the　ND-based　nanoplatform.　First,　the　NDs　were　modified　with　protamine　sulphate　(PS).　Meanwhile,　the　photosensitizer　indocyanine　green　(ICG)　and　the　HSP70　small　molecule　inhibitor　apoptozole　(APZ)　could　be　synchronously　incorporated　to　form　positively　charged　PS@ND　(ICG　+　APZ).　Then　negatively　charged　hyaluronic　acid　(HA)　was　assembled　onto　the　outer　face　of　PS@ND　(ICG　+　APZ)　to　form　the　NPIAs.　Finally,　the　positively　charged　small　molecule　anti-cancer　drug　doxorubicin　(DOX)　could　be　adsorbed　onto　the　surface　of　the　NPIAs　through　electrostatic　interactions　(NPIADs).　The　resulting　NPIADs　could　be　triggered　by　NIR　laser　irradiation　to　exhibit　enhanced　mild-temperature　photothermal　therapy　(PTT)　effects　via　suppressing　the　expression　of　HSP70,　and　PTT　combined　with　chemotherapy　could　further　enhance　the　anti-tumor　efficacy.　Subsequently,　the　sensitivity　of　MDA-MB-231　cells　could　be　significantly　improved　through　the　weakening　of　the　thermal/drug　resistance　via　autophagy　inhibition,　leading　to　augmented　combination　therapy　that　is　efficient　both　in　vitro　and　in　vivo.　Furthermore,　the　NPIADs　could　be　used　as　a　theranostic　nanoplatform　for　fluorescence　(FL)　and　photoacoustic　(PA)　imaging.　Taken　together,　this　study　demonstrated　a　multifunctional　ND-based　nanoplatform　for　FL/PA　imaging-guided　augmented　mild-temperature　photothermal/chemo　combination　therapy　via　an　autophagy　regulation　strategy　against　TNBC.