Paclitaxel　(PTX)　is　a　widely　used　anticancer　drug　that　works　by　inhibiting　microtubule　disassembly.　PTX　safety　was　greatly　enhanced　by　embedding　it　with　human　albumin.　Here,　we　study　the　synergistic　effects　of　PTX　with　photodynamic　therapy　(PDT)　both　in　vitro　and　in　vivo　by　constructing　photosensitizer-PTX　nanotheranostics　(PPNTs).　PPNTs　were　fabricated　via　noncovalent　hydrophobic　interactions　and　π-πstacking　between　an　amphipathic　photosensitizer　and　PTX　with　an　average　diameter　of　∼80　nm,　and　these　showed　high　stability　in　biological　conditions.　In　a　tumor-bearing　mouse　model,　PPNTs　were　shown　to　accumulate　at　the　tumor　site　based　on　three-dimensional　fluorescence　tomographic　imaging.　Under　680　nm　light　irradiation,　PPNTs　exhibited　a　superior　solid　tumor　ablation　effect　in　a　mouse　model,　with　a　dose　of　PTX　(0.2　mg/kg)　that　is　10-fold　lower　than　that　typically　used.　Mechanistically,　PPNTs　induced　a　strong　apoptotic　response　in　cells　under　light　illumination　and　showed　an　increased　antitumor　efficacy　that　is　47.2-fold　and　57.6-fold　higher　than　that　of　the　photosensitizer　nanoparticles　(PNTs)　and　free　PTX,　respectively.　In　addition,　PPNTs　showed　enhanced　cellular　uptake　with　focused　mitochondria　and　lysosome　colocalization　compared　to　that　of　PNTs　and　the　amount　of　PTX　delivered　in　PPNTs　was　sufficient　to　induce　cell　cycle　arrest　in　the　G2/M　phase.　These　findings　indicated　that　the　current　combination　therapy　has　advantages　over　monotherapy　in　promoting　tumor　regression　and　ultimately　achieving　tumor　elimination.　Copyright　©　2020　American　Chemical　Society.