Genetic information sensors play a pivotal role in the biomedical field. The detection of deoxyribonucleic acid (DNA) is achieved experimentally using an optical microfiber interferometric sensor, which operates based on an ion-regulation sensitivity enhancement mechanism. The optical microfiber is fabricated by drawing optical fiber into a diameter of less than 10 μm via the melting and tapering technique. Leveraging the characteristics of monovalent cations can effectively promote the folding of G-rich single-stranded DNA (ssDNA) into stable G-quadruplex structures, enabling the detection of specific sequences of ssDNA at low concentrations. The results show an improvement of the linear detection range by 3 orders of magnitude, and with the introduction of the ion-regulation sensitivity enhancement mechanism, the limit of detection (LOD) value is 1.07 × 10-15 M. This optical microfiber interferometric sensing architecture is characterized by its simplicity and high sensitivity, positioning it as a formidable tool for diverse biosensing and analytical applications.