Photothermal　therapy　(PTT)　and　sono-photodynamic　therapy　(SPDT)　are　fast　growing　local　treatment　modalities　with　minimal　invasiveness　and　high　safety.　Gold　nanoparticles　and　indocyanine　green　(ICG)　have　been　used　as　sensitizers　for　PTT　and　SPDT.　However,　long　resident　time　of　gold　nanoparticles　in　tissues　and　fast　elimination　of　ICG　hampered　their　further　clinical　applications.　Herein,　we　developed　nanocapsules　formed　by　hyaluronic　acid　and　chitosan　loading　with　ICG　and　tiny　gold　nanoclusters　(TAuNCs)　to　overcome　the　shortcomings　of　gold　nanoparticles　and　ICG　for　combined　PTT　and　SPDT.　The　nanocapsules　exhibited　good　biological　stability,　favorable　photothermal　effects,　and　ultrasound/near-infrared　light　(NIR)-responsive　release　behaviors.　The　hyaluronic　acid　could　mediate　the　specific　delivery　of　cargos　to　CD44　protein　over-expressing　cancer　cells.　The　in　vitro　and　in　vivo　results　showed　that　TAuNCs　and　ICG　could　act　synergistically　to　obtain　satisfactory　anticancer　effects　under　NIR　laser　and/or　ultrasound　exposure　induced　by　thermal　ablation　and　reactive　oxygen　species　(ROS)　generation.　Biodistribution　and　excretion　studies　showed　that　the　nanocapsules　had　longer　ICG　retention　time　in　tumor　and　most　of　the　TAuNCs　could　be　effectively　excreted　from　the　body　within　one　month.　This　study　thus　provides　a　facile　strategy　for　the　development　of　a　safe　and　high-performance　nanoplatform　for　synergistic　PTT/SPDT.　(C)　2022　Elsevier　Inc.　All　rights　reserved.