Glioblastoma,　accounting　for　44%　of　all　malignant　brain　tumors,　is　characterized　by　a　dismal　prognosis　due　to　high　mortality,　recurrence,　and　limited　survival　time.　Current　standard　treatment,　radiotherapy,　is　resistant　to　the　tumor　hypoxic　microenvironment,　which　reduces　the　effect　of　radiotherapy.　Here,　we　present　a　nanoplatform,　PLGA-Hemin@RBCM　(PHR),　which　leverages　the　catalase　mimetic　activity　of　hemin　to　convert　tumor-elevated　H2O2　into　oxygen　and　hydroxyl　radicals,　improving　tumor　oxygenation　and　enhancing　radiotherapy　sensitivity.　The　PEG-PLGA　nanomicelle　delivery　platform　improves　the　biocompatibility　and　stability　of　the　drug　and　delays　the　release　of　the　drug.　Camouflaging　the　nanoparticles　with　red　blood　cell　membranes　not　only　avoids　immune　clearance　but　also　prolongs　circulation　time　and　enhances　tumor　accumulation　via　the　EPR　effect.　In　vitro　and　in　vivo　studies　demonstrate　the　efficacy　of　our　nanoplatform,　offering　a　promising　therapeutic　strategy　for　glioblastoma　management　in　the　clinic.　©　2024　American　Chemical　Society.