A novel type of bio-nanoreactor with catalase loaded inside TaOx hollow nanoshells is fabricated via a mild one-step method. Such bio-nanoreactors could efficiently improve the tumor oxygenation by supplying oxygen via decomposition of endogenic H2O2 in a tumor microenvironment, and thus synergistically enhance the efficacy of cancer radiotherapy by both depositing radiation energy within the tumor and overcoming hypoxia-induced radiotherapy resistance.