Oxygen　deficiency　is　a　major　obstacle　to　hypoxic-related　cancer　theranostics,　and　developing　the　oxygen　production　nanoplatforms　received　the　widespread　attention.　However,　it　is　remaining　a　challenge　to　structure　a　nanoplatform　with　hypoxia　alleviation　effect　and　imaging-guided　cancer　radiotherapy.　Herein,　we　present　a　novel　theranostics　nanoplatform　(Au　NPs/UCNPs/WO3@C)　comprising　of　tungsten　trioxide　(WO3)　that　loaded　gold　nanoparticles　(Au　NPs)　and　up-conversion　nanoparticles　(UCNPs)　for　improved　photoacoustic　(PA)　imaging　performance　in　the　second　near　infrared　window　(NIR-II,　900–1,700　nm).　Au　NPs/UCNPs/WO3@C　exhibited　superior　oxygen-generation　effect　and　doxorubicin　loading　capacity,　thus　serving　as　an　efficient　radiosensitizer　for　radio-chemo　anti-cancer　therapy.　Importantly,　the　accumulated　Au　NPs/UCNPs/WO3@C　in　the　tumor　region　led　to　the　increased　NIR-II　PA　imaging　signal　and　the　blood　oxygen　saturation　signal,　which　could　enhance　radiation　sensitivity　and　accurately　guiding　cancer　radiotherapy　to　reduce　side　effects　on　normal　tissues.　This　study　with　proof-of-concept　confirmed　the　multifaceted　characteristics　and　encouraging　potential　of　biomimetic　Au　NPs/UCNPs/WO3@C　for　NIR-II　PA　imaging-guided　tumor　therapeutics.　[Figure　not　available:　see　fulltext.]　©　2021,　Tsinghua　University　Press　and　Springer-Verlag　GmbH　Germany,　part　of　Springer　Nature.