One phosphine oxide‐based pillar[5]arene 1a and two novel phosphorous‐based pillar[5]arenas 1b and 1c were synthesized for use as extractants in solvent extraction of UO22+. The results from host‐guest interactions pertinent to the extracted complexes of 1a–1c revealed a significant difference in complexation capability between 1a and 1b (or 1c) by using 1H NMR, 31P NMR and FT‐IR techniques. The extraction of UO22+ in separate extraction system and in simulated nuclear industry effluent containing 12 competing ions demonstrated the superior efficiency and selectivity of 1a towards UO22+ over other cations in acidic feed. Log‐log plot analysis indicated the 1:1 stoichiometry (ligand/metal) for the extracted complex formed between the ligand and UO22+.