Influenza viruses spread through the respiratory tract among humans, and it is particularly important to enhance the mucosal immunity against the viruses by vaccination, However, influenza vaccines, which are now mainly inactivated vaccines and inoculated by intramuscular injection, can hardly induce mucosal immunity. In this study, mucosal immunization of mice with H7N9 inactivated influenza vaccine was explored. In order to enhance effectiveness of the vaccine through ?intranasal route, phospholipids and cholesterol, whose properties are similar to those of pulmonary surfactants (PS), were used to prepare PS-biomimetic liposomes, and then resiquimod (R848), a small-molecule compound, was encapsulated within the bionic PS liposomes using thin-film dispersion method to form a novel mucosal adjuvant. BALB/c mice were immunized intranasally with H7N9 influenza inactivated vaccine mixed with PS-R848. The immunological indicators and protective effects post challenge were detected. Compared with the vaccine plus R848, the vaccine plus PS-R848 induced in mice significantly increased serum immunoglobulin G (IgG) antibody, IgG1 and IgG2a subclass antibody titers, haemagglutination inhibition (HI) titers, and lung secretory IgA titers, and also significantly increased secretion amounts of interferon-γ (IFN-γ), interleukin-2 (IL-2) and IL-4 cytokines. After the lethal homologous virus attack, mice in vaccine plus PS-R848 group survived 100%, with significantly reduced lung residual virus titer and the maximum weight loss rate, compared to the vaccine alone group. The results indicated that PS-biomimetic liposomes encapsulating R848 could be used as a mucosal adjuvant to effectively enhance the immune efficacy of inactivated influenza virus vaccines.