Centipedes can subdue giant prey by using venom, which is metabol-ically expensive to synthesize and thus used frugally throughefficiently disrupting essential physiological systems. Here, we showthat a centipede (Scolopendra subspinipes mutilans, ∼3 g) can sub-due a mouse (∼45 g) within 30 seconds. We found that this obser-vation is largely due to a peptide toxin in the venom, SsTx, andfurther established that SsTx blocks KCNQ potassium channels toexert the lethal toxicity. We also demonstrated that a KCNQ opener,retigabine, neutralizes the toxicity of a centipede’s venom. Thestudy indicates that centipedes’ venom has evolved to simulta-neously disrupt cardiovascular, respiratory, muscular, and nervoussystems by targeting the broadly distributed KCNQ channels, thusproviding a therapeutic strategy for centipede envenomation.