This paper describes chemically functionalized mesoporous silica as a novel catalyst for the rapid hydrolysis of a phenyl ester. Our study demonstrates a very simple and flexible approach to controlling the surface reactivity on the nanometer scale using a self-assembled organic monolayer consisting of polar(dihydroxyl, carboxyl, ethylene-diamine, and dihydroimidazole), and non-polar (isobutyl) groups. All five functional groups are essential requirements for preparing an enzyme-like catalyst because of their synergistic effect and hydrophobic partitioning, which we verified through 13 C CP-MAS solid state NMR spectroscopy. Catalytic activities were obtained from the catalytic efficiency constant and the specificity constant using Michaelis-Menten kinetics. Catalytic activities were close to those of a natural enzyme when 12% of the surface was covered by hydrophobic isobutyl silane. The rate of enzyme-catalyzed activity is dependent on the energy of the transition state, as defined in terms of an energy barrier derived from the relationship between the transfer free energy and the specificity constant.