A new synthetic route was developed to modify cellulose nanofiber for water-repellent coatings with great sustainability after multiple washing cycles. Multiple functional groups were grafted on 2,2,6,6-tetramethylpiperidine 1-oxyl radical (TEMPO)-oxidized cellulose nanofibers (TOCN) to achieve superhydrophobic performance and strong adhesion on cotton cloth. First, hexadecylamine (HDA) was used to modify TOCN surface into hydrophobic derivatives via amidation. The amidation-modified TOCN (AMT) were then grafted with a polyisocyanate cross-linking agent (PCA). The final multimodified TOCN (MMT) had hydrophobic alkyls and isocyanate groups on the surface. These surface functional groups were confirmed by Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS). After spraying the MMT suspension on cotton fabrics, the isocyanate groups would react with hydroxyl groups on cotton fibers, leading to a uniform conformal layer of MMT on fabric surfaces. The MMT coating showed great water repellence and washing sustainability. A large contact angle of 150 degrees and a small sliding angle of similar to 10 degrees were observed. The superhydrophobic performance retained even after 10 laundry washing cycles. Several examples were also demonstrated to show the capability and the possibility of applying this coating material for water-repellent applications.