We demonstrate a rationale for using GaN nanowires (GaNNWs) in label-free DNA-sensing using dual routes of electrochemical impedance spectroscopy (EIS) and photoluminescence (PL) measurements, employing a popular target DNA with anthrax lethal factor (LF) sequence. The in situ EIS reveals that both high surface area and surface band-bending in the nanowires, providing more binding sites and surface-enhanced charge transfer, respectively, are responsible for the enhanced sensitivity to surface-immobilized DNA molecules. The net electron-transfer resistance can be readily deconvoluted into two components because of the coexistence of two interfaces, GaN/DNA and DNA/electrolyte interfaces, in series. Interestingly, the former, decreasing with LF concentration (CLF), serves as a signature for the extent of hybridization, while the latter as a fingerprint for DNA modification. For PL-sensing, the band-edge emission of GaNNWs serves as a parameter for DNA modification, which quenches exponentially with CLF as the incident light is increasingly blocked from reaching the core nanowire by rapidly developing a UV-absorbing DNA sheath at high CLF. Furthermore, successful application for detection of "hotspot" mutations, related to the human p53 tumor-suppressor gene, revealed excellent selectivity and specificity, down to picomolar concentration, even in the current unoptimized sensor design/condition, and in the presence of mutations and noncomplementary strands, suggesting the potential pragmatic application in complex clinical samples.