Enterovirus 71 (EV71) is a highly infectious causative agent of hand, foot and mouth disease (HFMD) in children which could lead to severe neurological complications. There is currently no vaccine available against EV71. Thus vaccination is considered the most effective means to control EV71 infection. This study aims to develop a candidate vaccine in DNA vaccine platform. The immunogenicity of the constructed DNA vaccine was evaluated in BALC/c mice involving two delivery methods: as a naked DNA vaccine delivered intramuscularly and delivered orally via the live attenuated bacteria Salmonella typhi Ty21a. In conclusion, DNA vaccine used alone in a homologous prime boost approach or as the primer vaccine in a heterologous prime boost immunization show potential for further development as a vaccine against EV71.