Carmustine　(BCNU),　a　vital　type　of　chloroethylnitrosourea　(CENU),　inhibits　tumor　cells　growth　by　inducing　DNA　damage　at　O(6　)position　of　guanine　and　eventually　forming　dG-dC　interstrand　cross-links　(ICLs).　However,　the　clinical　application　of　BCNU　is　hindered　to　some　extent　by　the　absence　of　tumor　selectivity,　poor　stability　and　O-6-　alkylguanine-DNA　alkyltransferase　(AGT)　mediated　drug　resistance.　In　recent　years,　tumor　microenvironment　has　been　widely　utilized　for　advanced　drug　delivery.　In　the　light　of　the　features　of　tumor　microenvironment,　we　constructed　a　multifunctional　hypoxia/esterase-degradable　nanomicelle　with　AGT　inhibitory　activity　named　HACB　NPs　for　tumor-targeting　BCNU　delivery　and　tumor　sensitization.　HACB　NPs　was　self-assembled　from　hyaluronic　acid　azobenzene　AGT　inhibitor　conjugates,　in　which　O6-BG　analog　acted　as　an　AGT　inhibitor,　azobenzene　acted　as　a　hypoxia-responsive　linker　and　carboxylate　ester　bond　acted　as　both　an　esterase-sensitive　switch　and　a　connector　with　hyaluronic　acid　(HA).　The　obtained　HACB　NPs　possessed　good　stability,　favorable　biosafety　and　hypoxia/　esterase-responsive　drug-releasing　ability.　BCNU-loaded　HACB/BCNU　NPs　exhibited　superior　cytotoxicity　and　apoptosis-inducing　ability　toward　the　human　uterine　cervix　carcinoma　HeLa　cells　compared　with　traditional　combined　medication　of　BCNU　plus　O-6-BG.　In　vivo　studies　further　demonstrated　that　after　a　selective　accumulation　in　the　tumor　site,　the　micelles　could　respond　to　hypoxic　tumor　tissue　for　rapid　drug　release　to　an　effective　therapeutic　dosage.　Thus,　this　multifunctional　stimulus-responsive　nanocarrier　could　be　a　new　promising　strategy　to　enhance　the　anticancer　efficacy　and　reduce　the　side　effects　of　BCNU　and　other　CENUs.