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Glioma is the most common primary intracranial tumor without effective treatment. Positron emission tomography tracers labeled with 68Ga targeting fibroblast activation protein (FAP) have shown favorable characteristics in the diagnosis of glioma. However, to the best of our knowledge, FAP-targeted endoradiotherapy has never been explored in glioma. Hence, in this study, we investigated the therapeutic effect of 211At-labeled fibroblast activation protein inhibitor (FAPI) for glioma in vitro and in vivo. By astatodestannylation reaction, we prepared 211At-FAPI-04 with a radiochemical yield of 45 ± 6.7% and radiochemical purity of 98%. With good stability in vitro, 211At-FAPI-04 showed fast and specific binding to FAP-positive U87MG cells, and could significantly reduce the cell viability, arrested cell cycle at G2/M phase and suppressed cell proliferative efficacy. Biodistribution studies revealed that 6-fold higher accumulation in tumor sites was achieved by intratumoral injection in comparison with intravenous injection. In U87MG xenografts, 211At-FAPI-04 obviously suppressed the tumor growth and prolonged the median survival in a dose-dependent manner without obvious toxicity to normal organs. In addition, reduced proliferation and increased apoptosis were also observed after 211At-FAPI-04 treatment. All these results suggest that targeted alpha-particle therapy (TAT) mediated by 211At-FAPI-04 can provide an effective and promising strategy for the treatment of glioma.