In this manuscript we describe a guanidinium-modified zinc phthalocyanine (Zn-DIGP) that is the first example of a high-affinity G-quadruplex ligand exhibiting both “turn-on” luminescence and the ability to knock-down RNA expression. With a dissociation constant < 2 nM, the interaction between Zn-DIGP and c-Myc G-quadruplex DNA is the highest affinity G-quadruplex – small molecule binding interaction reported to date. Zn-DIGP’s luminescence properties allowed for direct DNA binding assays in vitro and its imaging in vivo. The cellular uptake and localization of Zn-DIGP was different from duplex DNA probes like Hoechst 33342, and at relatively low doses (1 uM) it caused a rapid 3-fold knock-down of c-MYC mRNA in neuroblastoma cells. The exact mechanism responsible for this knock-down is still under investigation, but our results are consistent with quadruplex-mediated promoter deactivation. Taken together, these results indicate that Zn-DIGP is a new tool uniquely suited to help decipher G-quadruplex structure and function.