We have demonstrated the influence of cerium dioxide nanoparticles on the immunogenicity of the influenza vaccine on an example of liquid split inactivated Vaxigrip vaccine. Antibody titers were analyzed using the hemagglutination inhibition (HI) assay. Seroprotection, seroconversion, the geometric mean titers (GMTs) and the factor increase (FI) in the GMTs were calculated. The effect of nano-ceria surface stabilizer on the enhancement of immunogenicity was shown. The vaccine modified by citrate-stabilized nano-ceria, in contrast to a non-modified Vaxigrip vaccine, did not provide an adequate level of seroprotection, and seroconversion after vaccination was 66.7% on days 49–63 for virus strain Α(H1N1) and 100% on day 49 for virus strain B/Yamagata. For the low immunogenic influenza B virus, the rise in antibody titers (GMT/IF) was 24.38/3.28 after the first injection and 50.40/6.79 on day 49. For the vaccine modified by non-stabilized nano-ceria, for all virus strains under study, on day 63, upon immunization notable levels of seroprotection, seroconversion and GMT/IF were registered (higher than for the non-modified Vaxigrip vaccine). The successful attempt to modify the influenza vaccine demonstrates the possible ways of increasing the specific activity of vaccines using nano-ceria.