Although reducible-oxide-supported gold nanostructures exhibit the highest CO oxidation activity at low temperatures, they are not suitable for preferential oxidation (PROX) reactions owing to their limited selectivity towards CO in the presence of H2. The interaction of the support and the metal has been proven to be the deciding factor for the selectivity as well as activity. Here, we demonstrate the possibility of selective CO oxidation using zinc-stannate-supported Au nanoparticles for the first time. The catalytic activity of the Zn2SnO4/Au hybrid for CO preferential oxidation in H2 gases was systematically investigated. The catalytic performance is closely correlated with the formed interfaces and the Zn2SnO4 support as well as the valence state of Au. Remarkably, we observed an exceptionally high activity with the spent Zn2SnO4/Au catalyst, which is usually unattainable for Au based materials due to the coarsening of Au nanoparticles. Careful in situ diffuse reflectance Fourier transform infrared (DRIFT) spectroscopy experiments of the hybrid led to the conclusion that the OH mediated pathway is the origin of enhanced activity. Overall, the support promotes hybrid activity under PROX conditions that is different from most of the reducible and non-reducible oxide supports. Our results represent a significant advance in the search for suitable supports for preferential CO oxidation with good selectivity as well as high activity. © 2016 The Royal Society of Chemistry.