Three phosphine oxide functionalized pillar[5]arenes (POP5A) were evaluated for the extraction of uranyl ion from nitric acid feed solutions in room temperature ionic liquid (RTIL), 1-n-octyl-3-methylimidazolium hexafluorophosphate (C(8)mimNTf(2)). The host-guest interaction between POP5A and C(8)mim(+) for the formation of [POP5A C(8)mim](+) complex was evidenced by 1D and 2D proton NMR spectroscopy and mass spectra technique before extraction, and also supported by theoretical calculation. High extraction efficiency and selective separation of UO22+ were achieved with the ligand bearing longer spacer exhibiting best solvent extraction performance. The distribution ratios of U(VI) in RTIL were significantly enhanced in the range of 0.1-1.8 M HNO3 as compared with organic diluent. The extracted species were ascertained from the slope analysis method as well as Job plots method, and a supramolecular cation-exchange mechanism involving competitive host-guest interactions was found to dominate the extraction process. This extraction system was also examined for its ability towards extraction of lanthanides and Th4+. The results revealed an excellent selectivity towards UO22+ over other metal ions. Stripping experiments showed almost a complete back extraction of UO22+ within four stages. With high selectivity towards UO22+ and efficient back extraction, this new POP5A-RTIL extraction system shows promise for future application of uranium recovery.