HighlightsA　narrow　bandgap　electron　donor-acceptor　(D-A)　semiconducting　polymer　nanoparticle　(SPN)　coated　with　red　blood　cell　membrane　(RBCM)　for　photoacoustic　imaging　and　photothermal　therapy.The　D-A　structure　endows　SPN　with　excellent　near-infrared　absorbance,　high　photothermal　conversion　ability,　and　good　photothermal　stability.The　RBCM　endows　SPN　with　good　biocompatibility,　prolonged　blood　circulation,　and　improved　tumor　accumulation,　while　the　small　size　structure　endows　SPN　with　deep　tumor　penetration　and　rapid　clearance　from　body.　AbstractSemiconducting　conjugated　polymer　nanoparticles　(SPNs)　represent　an　emerging　class　of　phototheranostic　materials　with　great　promise　for　cancer　treatment.　In　this　report,　low-bandgap　electron　donor-acceptor　(D-A)-conjugated　SPNs　with　surface　cloaked　by　red　blood　cell　membrane　(RBCM)　are　developed　for　highly　effective　photoacoustic　imaging　and　photothermal　therapy.　The　resulting　RBCM-coated　SPN　(SPN@RBCM)　displays　remarkable　near-infrared　light　absorption　and　good　photostability,　as　well　as　high　photothermal　conversion　efficiency　for　photoacoustic　imaging　and　photothermal　therapy.　Particularly,　due　to　the　small　size　(＜5　nm),　SPN@RBCM　has　the　advantages　of　deep　tumor　penetration　and　rapid　clearance　from　the　body　with　no　appreciable　toxicity.　The　RBCM　endows　the　SPNs　with　prolonged　systematic　circulation　time,　less　reticuloendothelial　system　uptake　and　reduced　immune-recognition,　hence　improving　tumor　accumulation　after　intravenous　injection,　which　provides　strong　photoacoustic　signals　and　exerts　excellent　photothermal　therapeutic　effects.　Thus,　this　work　provides　a　valuable　paradigm　for　safe　and　highly　efficient　tumor　photoacoustic　imaging　and　photothermal　therapy　for　further　clinical　translation.