The development of highly-efficient catalysts for conversion of glucose and fructose to 5-hydroxymethylfurfural (HMF) is of great importance. In this work, theoretical simulations form the basis for rational design and synthesis of a superhydrophobic mesoporous acid, that can completely prevent HMF hydration, giving HMF as sole product from full conversion of fructose. Interestingly, the combined superhydrophobic solid acid and superhydrophilic solid base catalysts are very efficient for one-pot conversion of glucose to HMF, giving a yield as high as 95.4 %. The excellent catalytic data in the conversion of glucose to HMF is attributed to the unique wettabilities of the solid acid and base catalysts.