objective: To create a novel subunit vaccine that used AuNPs as carriers to enhance immune responses in mice against recombinant classical swine fever virus E2 protein (CSFV E2). results: Gold nanoparticles (AuNPs) were successfully coupled to the E2 protein and formed stable particle complexes called E2 conjugated AuNPs (E2-AuNPs). In vitro studies have shown that the E2-AuNPs complex has the same immunogenicity as the E2 protein, and AuNPs can promote the phagocytosis of the E2 protein by antigen-presenting cells (APCs). In vivo results of BALB/c mice showed that the antibody levels, lymphocyte proliferation index, IFN-γ and IL-10 cytokines induced by E2-AuNPs were relatively higher than those of E2 or AuNPs group. conclusions: This finding demonstrated the potential of using AuNPs as a carrier to enhance the body's immune response for developing CSFV subunit vaccines. This model also contributes to the development of other flavivirus subunit vaccines, such as hepatitis C virus (HCV) and bovine viral diarrhea virus (BVDV).