Flooding is a widespread natural disaster that leads to oxygen (O 2) and energy deficiency in terrestrial plants, thereby reducing their productivity. Rice is unusually tolerant to flooding, but the underlying mechanism for this tolerance has remained elusive. Here, we show that protein kinase CIPK15 [calcineurin B-like (CBL)-interacting protein kinase] plays a key role in O2-deficiency tolerance in rice. CIPK15 regulates the plant global energy and stress sensor SnRK1A (Snf1-related protein kinase 1) and links O2-deficiency signals to the SnRK1-dependent sugar-sensing cascade to regulate sugar and energy production and to enable rice growth under floodwater. Our studies contribute to understanding how rice grows under the conditions of O2 deficiency necessary for growing rice in irrigated lowlands.