We demonstrate a novel electrochemical sensor for highly sensitive detection of natural double-stranded deoxyribonucleic acid (dsDNA) based on thionin (Th) attached to Mo6S9−XIX nanowires (MoSI NWs) self-assembled on a gold electrode. The sensing detection is based on a decrease of the voltammetric response of the immobilized Th due to the binding of Th with dsDNA through intercalation. MoSI NWs act as molecular connectors to provide an ampliﬁcation and conductive sensing platform for the electrochem-ical detection of dsDNA, because many sulfur atoms at the ends and sides of MoSI NWs permit covalent bonds to be formed with gold as well as MoSI NWs with negative charges allow electrostatic binding with Th. A determination limit of 0.62 ng/mL for dsDNAwith this novel sensor is achieved,which is three orders ofmagnitude lower than that in the absence ofMoSI NWs. The operation is simple and label-free.