Commercial cellulase Cellic CTec2 was immobilized by the entrapment technique in sol–gel matrices, and sol–gel entrapment with deposition onto magnetic nanoparticles, using binary or ternary systems of silane precursors with alkyl- or aryl-trimethoxysilanes, at different molar ratios. Appropriate tailoring of the sol–gel matrix allowed for the enhancement of the catalytic efficiency of the cellulase biocatalyst, which was then evaluated in the hydrolysis reaction of Avicel microcrystalline cellulose. A correlation between the catalytic activity with the properties of the sol–gel matrix of the nanobiocatalysts was observed using several characterization methods: scanning electron microscopy (SEM), fluorescence microscopy (FM), Fourier transform infrared spectroscopy (FT-IR) and thermogravimetric analysis (TGA/DTA). The homogeneous distribution of the enzymes in the sol–gel matrix and the mass loss profile as a function of temperature were highlighted. The influence of temperature and pH of the reaction medium on the catalytic performance of the nanobiocatalysts as well as the operational stability under optimized reaction conditions were also investigated; the immobilized biocatalysts proved their superiority in comparison to the native cellulase. The magnetic cellulase biocatalyst with the highest efficiency was reused in seven successive batch hydrolysis cycles of microcrystalline cellulose with remanent activity values that were over 40%, thus we obtained promising results for scaling-up the process.