Reaction efficiencies of biorefinery processes are universally low because of the severe side reactions at high substrate loading. Here, we show that the use of Sn-modified Al2O3 catalyst in ionic liquid EMIMBr enables the efficient conversion of glucose to 5-hydroxymethylfurfural (HMF) at substrate loading up to 35 wt %, with the HMF production rate exceeding that of the previous reported catalytic systems. The introduction of a small quantity of Sn species to Al2O3 could improve their Lewis acid amount and surface area but not result in the increase of Brmnsted acid and base density, beneficial for the glucose isomerization into fructose with reduced degradation of HMF catalyzed by Bronsted acid. Moreover, the ionic liquid EMIMBr and the deposition of humins on the catalyst play important roles for the stabilization of HMF under the evaluated temperature. The superior reaction efficiency is attributed to the cooperation action of the heterogenous catalyst with EMIMBr.