To expand the application of nanofibrillated cellulose (NFC), the increase of its hydrophobicity is considered to be critical. In the present work, hydrophobic NFC powder was prepared through chemical modification with alkyl ketene dimer (AKD). The results showed that when modifying the original NFC with an AKD loading of 0.7 g/g (based on dry cellulose) at 110 °C for 6 h, the AKD graft yield of approximately 40% (based on initial cellulose mass) was successfully achieved. The Fourier transform infrared spectroscopy and X-ray diffraction analysis showed that the grafting reaction mainly occurred on the fibre surface and the nanocrystal structure of cellulose was preserved after chemical modification. The thermogravimetric analysis results indicated the thermal stability increased with increasing the AKD graft yield. Scanning electron microscopy observations indicated that no significant differences in fibril morphology before and after AKD modification. Water contact angle measurements of the films produced from original and AKD-modified NFC powders demonstrated the significant increase in hydrophobicity of NFC after modification with AKD. Moreover, the hydrophobicity of AKD-modified NFC increased with increasing AKD graft yield.