The chemo-selective oxidation of bifunctional substrates via a supramolecular strategy has been achieved. IBX (o-iodoxybenzoic acid) oxidations of hydroxybenzyl alcohols produce the corresponding aldehyde and o-quinones, while the presence of HemiQ[6] can restrain the IBX oxidation of phenolic hydroxyl groups to afford the aldehyde product. The conversion and reaction rate are greatly affected by the structures of substrates, and the stereo effect and electronic effect play very important roles in the selective oxidation system. Various spectroscopies, including ¹H NMR (proton nuclear magnetic resonance), IR (infrared), and UV-vis (ultra violet-visible) have been employed to confirm the host–guest interaction of HemiQ[6] with hydroxybenzyl alcohols.