Foot-and-mouth disease (FMD) is an economically significant animal disease because of the speed of its transmission. Routine vaccination may not be effective for early protection in an outbreak situation. Small interfering RNA (siRNA) can be used as a rapid, effective, and an alternative antiviral approach. In this study, we screened 15 synthetic siRNAs to inhibit FMD virus replication in IBRS-2 cells and selected 10 siRNA sequences. Furthermore, we produced 7 adenoviruses expressing shRNA targeting conserved regions of FMDV, such as a leader sequence and nonstructural protein regions, and showed their antiviral effects. We compared the antiviral effects among them and compared between synthetic siRNAs and adenovirus-delivered siRNAs. In particular, the most efficient siRNA, $3C_2$, was the conserved sequence in the O, A, Asia 1, and C serotypes of FMDV and was located in the predicted loop structure. The pool of sequences including $3C_2$ and recombinant adenoviruses could be applied for multiple siRNAs and protection in a broad range of cells and animals.