As　a　clinical　anti-glioma　agent,　the　therapeutic　effect　of　carmustine　(BCNU)　was　largely　decreased　because　of　the　drug　resistance　mediated　by　O-6-alkylguanine-DNA　alkyltransferase　(AGT)　and　the　blood-brain　barrier　(BBB).　To　overcome　these　obstacles,　we　synthesized　a　BCNU-loaded　hypoxia/esterase　dual　stimulus-activated　nanomicelle,　abbreviated　as　T80-HACB/BCNU　NPs.　In　this　nano-system,　Tween　80　acts　as　the　functional　coating　on　the　surface　of　the　micelle　to　facilitate　transport　across　the　BBB.　Hyaluronic　acid　(HA)　with　active　tumor-targeting　capability　was　linked　with　the　hypoxia-sensitive　AGT　inhibitors　(O-6-azobenzyloxycarbonyl　group)　via　an　esterase-activated　ester　bond.　The　obtained　T80-HACB/BCNU　NPs　had　an　average　particle　size　of　232.10　+/-　10.66　nm,　the　zeta　potential　of　-18.13　+/-　0.91　mV,　and　it　showed　high　drug　loading　capacity,　eximious　biocompatibility　and　dual　activation　of　hypoxia/esterase　drug　release　behavior.　The　obtained　T80-HACB/BCNU　NPs　showed　enhanced　cytotoxicity　against　hypoxic　T98G　and　SF763　cells　with　IC50　at　132.2　mu　M　and　133.1　mu　M,　respectively.　T80　modification　improved　the　transportation　of　the　micelle　across　an　in　vitro　BBB　model.　The　transport　rate　of　the　T80-HACB/Cou6　NPs　group　was　12.37　%,　which　was　7.6-fold　(p＜0.001)　higher　than　the　micelle　without　T80　modification.　T80-HACB/BCNU　NPs　will　contribute　to　the　development　of　novel　CENUs　chemotherapies　with　high　efficacy.