Foot-and-mouth disease (FMD) is a highly contagious disease in cloven-hoofed animals and can cause a considerable socio-economic loss for affected countries. Interleukin-18 (IL-18) is a pleiotropic cytokine and plays important role in both the development of a functional immune system as well as the response of the organism to infection. In the present study, bovine IL-18 (BoIL-18), Foot-and-mouth disease virus VP1 and VP1/BoIL-18 fusion genes were cloned and expressed in pichia pastoris (P. pastoris) and subsequently immune effects were evaluated to study the immune enhancing effects of recombinant BoIL-18 (rBoIL-18) on FMD vaccination. The results showed that the genes encoding for BoIL-18, VP1 and VP1/BoIL-18 are successfully expressed in P. pastoris and the expressed recombinant VP1 (rVP1) proteins could induce both humoral and marginal cell-mediated immune responses in mice, while the co-inoculation with rBoIL-18 could markedly enhance both of immune responses, and the inoculation of the fusion product rVP1/BoIL-18 showed even more dramatic immune responses, suggesting rBoIL-18 has a potential to enhance the efficacy of vaccination against FMDV infection.