[Objective] This study is to research the influence of foot-and-mouth disease virus (FMDV) leader protein for virus infectivity. [Methods] Two full-length infected cDNA clones were constructed based on O/HN/93 strain cDNA using reverse genetic technique which contain the leader protein of Chinese isolates O/CHN/Mya98/33-P and O/CHN/Mya98/HN1. Though real-time fluorescent quantitative PCR detecting the situation of IFNβ and OAS mRNA transcription, when pig kidney primary cells were infected the two different chimeric viruses. [Results] We found that the proliferation ability of chimeric virus rOHN1Lab is weaker, and the content of IFNβ and OAS it induced is higher. However, the proliferation ability of chimeric virus rO33Lab relative to rOHN1Lab is higher, and the content of IFNβ and OAS which induced is lower. [Conclusion] This study suggests that the leader protein of the Foot and mouth disease Chinese isolates O/CHN/Mya98/33-P have the stronger ability to resist IFNβ mRNA transcription, which lay the foundation for further identification of FMDV leader protein critical sites for resisting host innate immunity.