Due to the molecular and cellular heterogeneity of glioma, discov­ery of novel targeted sites and ligands for glioma imaging and therapy remains challenging. Neuropeptide Y (NPY) Y1 receptors (Y1Rs) are highly over expressed in various brain tumors including glioma, and can serve as potential targeting sites for glioma imaging and therapy. Here, we show by in vivo fluorescent imaging that a highly selective Y1R ligand, [Asn⁶,Pro³⁴] NPY (AP-NPY), facilitated circumvention of the blood brain barrier (BBB) by nano­micelles specifically targeting glioma. Modification with AP-NPY stabilized doxorubicin-loaded nanomicelles in the normal physio­logical state and promoted drug release in the acidic tumor micro-environment. Furthermore, targeted delivery of AP-NPY nano­micelles improved the therapeutic efficacy of doxorubicin for glioma, producing a prolonged survival rate. These results suggest that Y1R is a novel targeted receptor, and its selective ligand AP-NPY improves BBB permeability and glioma targeting. Our study paves the way for developing a novel delivery system for diagnosis and treatment of glioma in which Y1Rs are over expressed.