Chitosan is a non-toxic biological material, but chitosan is insoluble in water, which hinders the development and utilization of chitosan. Chitosan derivatives -2-Hydroxypropyl trimethyl ammonium chloride (-2-HACC) and carboxymethyl chitosan (CMCS) with good water solubility were synthesized by our laboratory. In this study, we synthesized mesoporous SiO nanoparticles by the emulsion, and then the mesoporous SiO nanoparticles were modified with γ-aminopropyltriethoxysilane to synthesize aminated mesoporous SiO nanoparticles; CMCS and -2-HACC was used to cross-link the aminated mesoporous SiO nanoparticles to construct SiO@CMCS--2-HACC nanoparticles. Because the aminated mesoporous SiO nanoparticles with positively charged can react with the mucous membranes, the virus enters the body mainly through mucous membranes, so Newcastle disease virus (NDV) was selected as the model drug to evaluate the performance of the SiO@CMCS--2-HACC nanoparticles. We prepared the SiO@CMCS--2-HACC nanoparticles loaded with inactivated NDV (NDV/SiO@CMCS--2-HACC). The SiO@CMCS--2-HACC nanoparticles as delivery carrier had high loading capacity, low cytotoxicity, good acid resistance and bile resistance and enteric solubility, and the structure of NDV protein encapsulated in the nano vaccine was not destroyed. In addition, the SiO@CMCS--2-HACC nanoparticles could sustain slowly released NDV. Therefore, the SiO@CMCS--2-HACC nanoparticles have the potential to be served as delivery vehicle for vaccine and/or drug.