Foot-and-mouth disease virus (FMDV) belongs to the aphthovirus genus within the picornavirus which has a single copy of a positive sense RNA. The translation initiation process of FMDV occurs by a cap-independent mechanism directed by a highly structured element (∼435 nt) termed an internal ribosome entry site (IRES). We have designed and prepared FMDV 4-2 RNA (28nt) by in vitro transcription. The 2D NMR data revealed that FMDV 4-2 IRES domain RNA has a flexible loop and bulge conformation. In further study, we need to make an isotope labeled RNA sample and conduct 3D NMR experiments to completely determine the 3D structure. This study may establish a new drug design strategy to treat foot-and mouth disease.