An environmentally friendly procedure for the chemical modification of cellulose nanocrystals (CNCs), obtained from pine wood, was developed to manufacture hydrophobic CNCs. In comparison to other methods, this procedure has the particularity of producing a hydrophobic CNC in a single step, without using organic solvents while using MTMS as a precursor. CNCs were successfully dispersed in water, and the NMR technique was used to study the hydrolysis reaction of the MTMS in water before the surface modification of the CNCs. After 24 h of the modification reaction, the spray-drying method was used to produce a dry powder of modified CNCs. The obtained hydrophobic CNCs were characterized by several techniques. FTIR spectroscopy confirmed the covalent bonds between the MTMS and CNCs as well as the formation of nanostructured polymethylsilsesquioxane (PMSQ) on the surface of the CNCs. XPS spectroscopy examined the presence of Si atoms of the MTMS on the surface of the CNCs. XRD detected the presence of a crystalline structure of PMSQ on the surface of the CNCs and confirmed the preservation of the CNCs crystal after the modification operation. The morphology study using SEM, AFM, and TEM techniques confirmed the presence of nanostructured PMSQ on the surfaces of modified CNCs. The hydrophobic CNCs showed a significant increase in water contact angle (110 degrees) compared to that of unmodified CNCs (43 degrees). This new way of modifying CNCs can produce hydrophobic CNCs with potential for dispersion in non-polar polymers for the formulation of new nanocomposites.