Virus-like particles(VLPs) represent a safe and effective vaccine platform, improving assembly efficiency is necessary to reduce the cost of vaccine production, and elicit a strong immune response. In this study, CpG and Poly(I:C) were selected as scaffolds to facilitate the assembly of FMDV VLPs in vitro. The particle size, surface potential, gel retardation assay, nuclease digestion experiments, size-exclusion chromatography, transmission electron microscopy and circular dichroism analysis showed that CpG and Poly(I:C) were successfully encapsulated inside of VLPs, and have no effect on shape and sizes. The peak area of 75S of co-assembled CpG-VLPs and Poly(I:C)-VLPs were significantly increased than FMDV-VLPs(P<0.0001). With increasing the assembly efficiency of CpG-VLPs and Poly(I:C)-VLPs, higher neutralizing antibodies were elicited. Although, CpG or Poly(I:C) as adjuvant enhanced the proliferation level of spleen lymphocytes, but the proportion of CD4+ T cells and CD8+ T cells in the lymphocyte were significantly increased after stimulating by co-assembled CpG-VLPs (P<0.01) and Poly(I:C)-VLPs (P<0.001). This study demonstrated that CpG and Poly(I:C) not only improved the assembly efficiency of FMDV VLPs, also had an adjuvant activity to enhance the immune response, Furtherly, proposes a new idea and optimized strategy for improving the assembly efficiency of VLPs and contributes to the development of VLPs vaccine.