Here a new reinforcement and mold-resistant method for ancient books is proposed based on the suspension of nanocellulose (CNCS) and polyhexamethylene guanidine (PHMG). The paper documents were treated with the reinforcement suspension under the optimum ratio obtained by response surface methodology (RSM), then tested for mildew resistance and accelerated aging experiments to evaluate the anti-mildew effect, mechanical strengthening properties and durability of CNCS/PHMG compound solution on ancient books. The results showed the mechanical properties of the paper treated by CNCS/PHMG were significantly improved at the optimum ratio (0.3 wt%:0.3 wt%), with the folding endurance increased by 1.78 times and the increase ratio of tensile strain was 46.62%. Meanwhile, the treated paper maintained the same good zero-span tensile strength after aging 7 days as the sample unaged untreated, indicating superior aging resistance of this treatment method. In addition, excellent biocidal activity with the growth trace of mold less than 10% was observed on treated paper. In conclusion, it is a method that simple to operate, which can be a promising treatment of conservation and enhancement of ancient paper.