Two mesoporous silica nanoparticles (MSNs) with different particle size, pore size, and surface area were synthesized and utilized as scaffolds for the immobilization of cellulase, an enzyme that can hydrolyze cellulose in aqueous solution. Two different immobilization methods, i.e., physical adsorption and chemical binding, were used to immobilize cellulase. The reaction conditions, including temperature, time, and the amount of cellulase for cellulosic hydrolysis, were optimized. This study systematically investigates the loading amount, catalytic activity, and stability of cellulase immobilized MSN catalysts. Results show that the cellulase chemically linked to MSN exhibiting carboxyl groups and a large pore size could achieve an effective cellulose-to-glucose conversion exceeding 80% yield and excellent stability.