Using single molecule fluorescence resonance energy transfer, we investigated the interaction between a quadruplex-binding ligand and the human telomeric G-quadruplex. The binding of quinolinecarboxamide macrocycle to telomeric DNA was essentially irreversible and selectively induced and favored one quadruplex conformation. The ligand-quadruplex complex displayed intramolecular dynamics including quadruplex folding and unfolding in the absence of ligand association and dissociation. We report that the G-quadruplex can be stabilized without preventing the-intrinsic intramolecular dynamics of telomeric DNA.