Tumor　microenvironment　is　characterized　by　low　pH,　high　reactive　oxygen　species　and　hypoxia,　which　provides　a　suitable　environment　for　cancer　growth.　The　hypoxia　not　only　elevates　tumor　angiogenesis　and　metastasis,　but　also　is　responsible　for　the　development　of　treatment　resistance,　which　gradually　becomes　a　significant　impediment　for　cancer　therapy.　Therefore,　we　developed　a　biomimetic　nanosystem　containing　hemoglobin　extracted　from　red　blood　cells,　chemotherapy　drug　sorafenib,　sensitizer　ursolic　acid　and　photosensitizer　indocyanine　green　for　enhanced　chemo-photo　combination　therapy　of　hepato-cellular　carcinoma,　which　could　not　only　enhance　the　chemotherapy　effect　of　sorafenib　bowing　to　the　sensitizing　effect　of　ursolic　acid,　but　also　achieved　synergetic　phototherapy　in　virtue　of　indocyanine　green.　Besides,　the　nanoparticles　could　effectively　delivery　exogenous　oxygen　to　tumor　site　and　amelio-rate　the　tumor　hypoxic　environment　with　the　assistance　of　hemoglobin.　The　dual-sensitization　drug　delivery　system　was　expected　to　effectively　reduce　the　resistance　of　traditional　treatment　methods　against　tumor　hypoxia,　providing　a　novel　prospect　for　the　synergistic　hepatocellular　carcinoma　treatment.(c)　2023　The　Korean　Society　of　Industrial　and　Engineering　Chemistry.　Published　by　Elsevier　B.V.　All　rights　reserved.