Here we demonstrate an anionic porphyrin, protoporphyrin IX (PPIX), as a parallel G-quadruplex-specific fluorescent probe for monitoring DNA structural changes and utilize it to develop a DNA-based K(+) sensor. The interactions of PPIX with different DNA structures in K(+) or Na(+) solution are investigated by using circular dichroism, fluorescence, and UV-vis spectroscopy. The observations reveal that PPIX has an ∼100-fold selectivity for parallel G-quadruplexes against duplexes and antiparallel G-quadruplexes. Meanwhile, the fluorescence intensity of PPIX increases by over 10-fold upon binding to parallel G-quadruplexes. On the basis of the selectivity and fluorescence property of PPIX, we introduce a facile, label-free approach to monitoring DNA structural changes via fluorescence signal readout that is tuned by PPIX binding and release. To illustrate it, we utilize PPIX and a G-rich DNA PS2.M to construct a fluorescent K(+) sensor based on an antiparallel-to-parallel conformation transition of the G-quadruplex. PS2.M adopts an antiparallel quadruplex structure in Na(+) solution, whereas it gradually converts into a parallel G-quadruplex upon addition of increasing K(+). This conformational change is indicated by a sharp increase in the fluorescence intensity of PPIX, owing to the good ability of PPIX to discriminate parallel G-quadruplexes from antiparallel ones. Even in the presence of 100 mM Na(+), such a "turn-on" fluorescent sensor can respond to low concentrations of K(+), with a limit of detection (0.5 mM) for K(+) analysis. In addition, this sensor exhibits a high selectivity for K(+) over other common metal ions, which ensures its practical applications to real samples. These results reveal that PPIX is promising for use as a specific DNA structural probe in sensing applications.