Hydrophobic nanofibrilated cellulose (NFC) films were prepared by the casting of a mixture of NFC suspension in an aqueous emulsion of two blocked isocyanates - one prepared by the reaction of 4,4′- methylenebis (phenyl isocyanate) and phenol (MDI-2Ph) and a commercial one from trimethylol propane and toluene diisocyanate (Desmodur AP Stabil®) (TMP-TDI-3Ph),). The drying procedure was performed in two steps, i.e., first at 60 °C for 24 h and then at 170 °C for 10 min. Infrared spectroscopy (FT-IR), elemental analysis, and 13 Csingle bondNMR confirmed the chemical modification of cellulose. The NFC modified films showed an approximately 40 g m−2.day−1 water vapor transmission rate, which is almost 75% lower than that of non-modified NFC films (153 g m−2.day−1). The film modified with TMP-TDI-3Ph showed a very low oxygen transmission rate and lower than that with MDI-2Ph When exposed to a wet environment, the modified films maintained their stiffness with Young's modulus around 5 GPa, whereas that of non- modified films decreased from approximately 6.5 GPa to below 0.1 GPa.