Paper is an inherent hydrophilic material due to the hydroxyl groups contained in cellulose, which limits its applications in packaging materials. This study proposed a simple one-step method for preparing hydrophobic paper by introduction of chitin nanocrystals (ChNCs) and hexadecyltrimethoxysilane (HDTMS). The surface chemistry and morphology of coated paper were studied in detail. The 2%ChNCs/HDTMS coated paper was highly hydrophobic with a water contact angle greater than 130°, mainly due to the low surface energy provided by HDTMS. Compared with uncoated paper, the hydrophobic paper's tensile strength and water vapor barrier are significantly improved due to the addition of ChNCs. Meanwhile, the hydrophobic paper shows excellent environmental tolerance and mechanical stability. The survival rate of L929 cells on the modified paper was more than 80% by CCK-8 assay, which proved that the nanocoating was safe. In addition, the obtained hydrophobic coated paper can hold water, cola, green tea, milk, coffee, and orange juice for a long time and can be used as a straw to absorb liquid. This work prepared high-performance and green hydrophobic paper, which exhibits wide applications in food packaging. • Hydrophobic paper coated with ChNCs/HDTMS was fabricated by one-step method. • ChNCs/HDTMS enhanced water vapor barrier and mechanical properties of paper. • The coated paper exhibited excellent environmental tolerance. • Hydrophobic paper showed antibacterial adhesion and satisfied biocompatibility. • The hydrophobic paper can be made into straw and paper cup.