Panic is an episode of strong defensive state, characterized by intense fear and severe physical symptoms such as elevated cardiorespiratory activities. How the brain generates panic state remains poorly understood. Here, we developed a robot-based experimental paradigm to evoke panic-like defensive state in mice. When stimulated by the robot, mice exhibited jumping escapes and elevated cardiorespiratory activities. With this paradigm, we identified Cbln2-expressing (Cbln2⁺) neurons in the posterior hypothalamic nucleus (PHN) as a key neuronal population essential for the induction of panic-like defensive state. Activation of Cbln2⁺ PHN neurons induced behavioral and physical symptoms of panic-like defensive state. These neurons were strongly activated by noxious mechanical stimuli and encode jumping escape vigor. They were synaptically innervated by anxiety-associated brain areas and provoked panic-like defensive state via their projection to the periaqueductal gray. Together, our results reveal a molecularly defined circuit module that regulates the panic-like defensive state in mice.