Numerous studies have reported cation dependent stability and topological changes of G-quadruplexes (G4s), but competitions between cations at different concentrations for binding with G4s and their effects on the polymorphism of G4 have been rarely investigated, which greatly limited the application of G4. Herein, with PW17 (a G4-forming DNA sequence) as a model system, the competition between K+ and Pb2+ for binding to G4 was clarified. Using a combination of circular dichroism and electrospray ionization mass spectroscopy, it was found that 10 mu M Pb2+ could replace K+ in K+-stabilized PW17 (2K(+)-PW17), but the substitution efficiency is highly dependent on K+ concentration (0.5-10 mM). In contrast, K+ at <10 mM could partly replace Pb2+ in stable and antiparallel Pb2+-stabilized PW17 (Pb2+-PW17) and completely substitute Pb2+ at K+ >= 10 mM. In these competing processes, a novel intermediate consisting of a Pb2+ and a K+ in the same G4 (K+-Pb2+-PW17) was first discovered, which acted as a bridge to achieve the switches. Through measuring the energetics of different concentrations of K+- and Pb2+-induced conformations, such a competitive binding was found to be thermodynamically permitted.