Most　treatments　for　spinal　cancer　are　accompanied　by　serious　side　effects　including　subsequent　tumor　recurrence,　spinal　cord　compression,　and　tissue　adhesion,　thus　a　highly　effective　treatment　is　crucial　for　preserving　spinal　and　neurological　functionalities.　Herein,　trilayered　electrospun　doxorubicin@bovine　serum　albumin/poly(ϵ-caprolactone)/manganese　dioxide　(DOX@BSA/PCL/MnO2)　nanofibers　with　excellent　antiadhesion　ability,　dual　glutathione/hydrogen　peroxide　(GSH/H2O2)　responsiveness,　and　cascade　release　of　Mn2+/DOX　was　fabricated　for　realizing　an　efficient　spinal　tumor　therapy.　In　detail,　Fenton-like　reactions　between　MnO2in　the　fibers　outermost　layer　and　intra-/extracellular　glutathione　within　tumors　promoted　the　first-order　release　of　Mn2+.　Then,　sustained　release　of　DOX　from　the　fibers＇　core　layer　occurred　along　with　the　infiltration　of　degradation　fluid.　Such　release　behavior　avoided　toxic　side　effects　of　drugs,　regulated　inflammatory　tumor　microenvironment,　amplified　tumor　elimination　efficiency　through　synergistic　chemo-/chemodynamic　therapies,　and　inhibited　recurrence　of　spinal　tumors.　More　interestingly,　magnetic　resonance　and　photoacoustic　dual-modal　imaging　enabled　visualizations　of　tumor　therapy　and　material　degradation　in　vivo,　achieving　rapid　pathological　analysis　and　diagnosis.　On　the　whole,　such　versatile　hierarchical-structured　nanofibers　provided　a　reference　for　rapid　and　potent　theranostic　of　spinal　cancer　in　future　clinical　translations.　©　2022　American　Chemical　Society.　All　rights　reserved.