Sonodynamic therapy (SDT) exhibits high tissue penetration and negligible radiation damage to normal tissues, and thus emerges as a promising cancer therapeutic modality for glioblastoma (GBM). However, the blood−brain barrier (BBB) and hypoxic microenvironment greatly limit the SDT efficiency. In this work, a biodegradable nanoplatform (termed as CSI) is fabricated by encapsulating catalase (CAT) into silica nanoparticles (CAT@SiO2) for tumor hypoxia relief, and then loaded with the sonosensitizer indocyanine green (ICG). Inspired by the ability of macrophages to cross the BBB, CSI is further coated with AS1411 aptamer-modified macrophage exosomes to form CSI@ Ex-A, which possesses efficient BBB penetration and good cancer-cell-targeting capability. After tumor cell endocytosis, highly expressed glutathione (GSH) triggeres biodegradation of the nanoplatform and the released CAT catalyzes hydrogen peroxide (H2O2) to produce O2 to relieve tumor hypoxia. The GSH depletion and O2 self-supplying effectively enhances the SDT efficiency both in vitro and in vivo. In addition, the resulting CSI@Ex-A exhibits good biocompatibility and long circulation time. These findings demonstrate that CSI@Ex-A may serve as a competent nanoplatform for GBM therapy, with potential for clinical translation.