Separating traces of cesium from aqueous medium containing large sodium amounts is a difficult problem because cesium and sodium ions have a similar behavior in aqueous medium. We selected a highly cesium-selective ligand in aqueous medium, and we determined the best conditions for using this ligand in a nanofiltration-complexation process in order to achieve Cs+/Na+ separation. We also tried to find a relation between the ligand structure and its activity toward cesium complexation. Tetrahydroxylated bis-crown-6 calix[4]arene was found to be very cesium selective (S = beta(Cs+)/beta(Na+) = 6600). Combined with a nanofiltration process, this ligand helped reaching 90% cesium retention in;a highly concentrated aqueous medium ([NaNO3] = 3 mol/L).