The　permeability　of　the　highly　selective　blood-brain　barrier　(BBB)　to　anticancer　drugs　and　the　difficulties　in　defining　deep　tumor　boundaries　often　reduce　the　effectiveness　of　glioma　treatment.　Thus,　exploring　the　combination　of　multiple　treatment　modalities　under　the　guidance　of　second-generation　near-infrared　(NIR-II)　window　fluorescence　(FL)　imaging　is　considered　a　strategic　approach　in　glioma　theranostics.　Herein,　a　hybrid　X-ray-activated　nanoprodrug　was　developed　to　precisely　visualize　the　structural　features　of　glioma　microvasculature　and　delineate　the　boundary　of　glioma　for　synergistic　chemo-radiotherapy.　The　nanoprodrug　comprised　down-converted　nanoparticle　(DCNP)　coated　with　X-ray　sensitive　poly(Se-Se/DOX-co-acrylic　acid)　and　targeted　Angiopep-2　peptide　(DCNP@P(Se-DOX)@ANG).　Because　of　its　ultrasmall　size　and　the　presence　of　DOX,　the　nanoprodrug　could　easily　cross　BBB　to　precisely　monitor　and　localize　glioblastoma　via　intracranial　NIR-II　FL　imaging　and　synergistically　administer　antiglioblastoma　chemo-radiotherapy　through　specific　X-ray-induced　DOX　release　and　radiosensitization.　This　study　provides　a　novel　and　effective　strategy　for　glioblastoma　imaging　and　chemo-radiotherapy.