Abstract: For Bcl-2, VEGF, c-Myc oncogene promoter, we directly observed that the G-rich sequences preferentially adopt G-quadruplex structures by ESI-MS. And the non-covalent interaction of the G-quadruplexes and 34 small molecules was investigated. The dimeric G-quadruplex structures of HIV-1 IN inhibitors were detected by ESI-MS for the first time. We observed the specific binding of a perylene derivative, which could shift the equilibrium to the dimeric G-quadruplex, while the polyamide induced a structural change to the intramolecular one.