Currently,　it　is　still　a　challenge　to　develop　an　organic　photosensitizer　(PS)　with　outstanding　near-infrared　absorption,　low　O2　dependence,　precise　tumor　targeting　and　rapid　clearance　through　the　kidney　to　improve　the　overall　outcome　of　phototherapy.　In　this　study,　we　have　designed　an　organic　PS　(NcPB)　with　an　excellent　near-infrared　light　absorption　through　a　refined　molecular　strategy.　Meanwhile,　NcPB　was　assembled　into　nanoparticles　with　different　sizes　(NanoNcPB-1　and　NanoNcPB-0)　by　a　supramolecular　modulation　strategy.　As　the　results,　the　nanoparticle　with　an　ultra-small　size　(NanoNcPB-1)　generated　a　large　number　of　superoxide　anion　(O2　center　dot-)　in　a　low-O2　-dependent　manner　and　release　plenty　of　heat.　Furthermore,　the　results　of　in　vivo　experiments　demonstrated　that　NanoNcPB-1　actively　accumulated　in　tumor　tissues　and　showed　a　92　%　tumor　inhibition　after　photodynamic　and　photothermal　combination　therapy.　More　importantly,　NanoNcPB-1　could　be　rapidly　cleared　from　the　body　of　mice　via　the　renal　pathway,　which　alleviates　potential　side　effects　of　prolonged　retention　of　PS　in　the　circulation.　(c)　2025　Published　by　Elsevier　B.V.　on　behalf　of　Chinese　Chemical　Society　and　Institute　of　Materia　Medica,　Chinese　Academy　of　Medical　Sciences.