The innate defensive behaviors triggered by environmental threats play a critical role in animal survival. Among these behaviors, defensive attack physically toward threatening target (e.g. predator) is the last line of defense to struggle for survival. How the brain transforms threat-relevant sensory information into the action of defensive attack remains poorly understood. We found that noxious mechanical force in an inescapable context was a key stimulus to trigger defensive attack in laboratory mice. The mechanically-evoked defensive attack was abrogated by photoinhibition of vGAT+ neurons in the anterior hypothalamic nucleus (AHN). The AHN vGAT+ neurons encoded the intensity of mechanical force and were innervated by brain areas related to pain and attack. Activation of these neurons triggered biting attack toward predator, while suppressing other ongoing behaviors. The efferent pathway from AHN vGAT+ neurons to the periaqueductal gray was both sufficient and necessary for mechanically-evoked defensive attack. Together, these data revealed a GABAergic brain circuit engaged in converting noxious mechanical stimuli to neural signals that provoke defensive attack in mice.