The separation of styrene (St) and ethylbenzene (EB) mixtures is important in the chemical industry. Here, we explore the St and EB adsorption selectivity of two pillar-shaped macrocyclic pillar[n]arenes (EtP5 and EtP6; n = 5 and 6). Both crystalline and amorphous EtP6 can capture St from a St-EB mixture with remarkably high selectivity. We show that EtP6 can be used to separate St from a 50:50 v/v St:EB mixture, yielding in a single adsorption cycle St with a purity of >99%. Single-crystal structures, powder X-ray diffraction patterns, and molecular simulations all suggest that this selectivity is due to a guest-induced structural change in EtP6 rather than a simple cavity/pore size effect. This restructuring means that the material "self-heals" upon each recrystallization, and St separation can be carried out over multiple cycles with no loss of performance.