In the present work, modification of oleate-capped upconverting nanoparticles (OA@UCNPs) with AS1411 Gquadruplex DNA by a one-pot aqueous strategy was presented. The G-quadruplex structure of AS1411 and structural alterations upon interaction with OA@UCNPs were investigated by circular dichroism spectroscopy. The thermodynamic data of interaction was determined by isothermal titration calorimetry. The noncovalent interactions between OA@UCNPs and AS1411 were found to be exothermic and the negative value of Gibbs free energy confirmed the spontaneous nature of interaction. The size and surface charge of UCNPs were assessed using zeta-sizer and zeta-potential. The nanostructures were also characterized by FTIR, XPS, XRD, AFM, SEM and TEM analysis. The up-conversion efficiency of DNA-modified UCNPs was not significantly reduced in aqueous solution compared to hydrophobic ones in organic medium. The facile strategy described here made the modification more accessible to biologists and others by performing it only in aqueous media and avoiding extra steps such as bioconjugations using heterobifunctional cross-linkers.