Pyroptosis provides a new direction and broad prospects for cancer immunotherapy. However, the development of nanoplatform as pyroptosis inducers is limited, the discovery of a new type of nano-pyroptosis inducer for cancer immunotherapy is still imminent. Herein, the biodegradable Ca 2+ nanomodulators (CaNMs) are prepared as pyroptosis inducers for cancer immunotherapy via mitochondrial Ca 2+ overload . The obtained CaNMs can decompose under low pH to release Ca 2+ and curcumin, leading to a sudden surge in mitochondrial Ca 2+ ions，eventually resulting in pyroptosis. We not only confirm the happening of mitochondrial Ca 2+ overload-triggered pyroptosis for the first time but also reveal the robust immune responses via CaNMs, along with remarkably suppressing tumor proliferation and lung metastasis. This work will provide new strategies and inspirations for pyroptosis-mediated cancer treatments, greatly contributing to the further development of Ca 2+ nanomodulators.