In this study, cellulose nanofibers (CNFs) were crossed-linked with glutaraldehyde (GA) under acid condition for tailoring the mechanical properties and water-resistance of nanopaper or films. The impact of carboxyl content of CNFs, GA concentration, temperature, pH, and reaction time on the crosslinking was investigated, and the process conditions for the crosslinking were optimized. FT-IR analyses showed that CNFs/GA cross-linked nanopaper was successfully fabricated by acetalization between the -OH groups of CNFs and the -CHO groups of GA, resulting in the formation of a dense, three-dimensional network. The elastic modulus of CNFs/GA cross-linked film was 7.66GPa, 62.98% higher than that of CNFs film. The water-resistance of the cross-linked CNFs/GA films was improved. The crossed-linked CNFs/GA films was still intact after 24 h after being immersed in water, while the CNFs films almost dissolved completely after 20 min of soaking in water. This method provides a facile route to enhance the elastic modulus and water-resistance of CNFs for potential applications including bullet-proof glass interlayer, flexible electronic device, and new packing materials.