Cellulose nanocrystals (or whiskers) and microfibrillated cellulose (MFC) were successfully obtained from sisal fibers and modified with n-octadecyl isocyanate (C(18)H(37)NCO) using two different methods with one innovation that consists of an in situ solvent exchange procedure. The surface chemical modification was characterized by elemental analysis, as well as FTIR and XPS spectroscopies. The crystalline structure of both unmodified and modified nanoparticles was investigated through X-ray diffraction measurements. It was shown that the efficiency of the chemical modification is strongly dependent on the nature of the nanoparticle with explanation linked to specific area, ability of peeling, and solvent dispersion. The surface chemical modification with n-octadecyl isocyanate allows dispersion of the nanoparticles in organic solvents and may allow processing of nanocomposite films from a casting/evaporation technique for a broad range of polymeric matrices.