Abstract: To screen the optimum siRNA targeting porcine integrin αV subunit as FMDV receptor against FMDV replication, three siRNA sequences were selected according to porcine integrin αV mRNA sequence, the complementary DNA contained both sense and antisense oligonucleotides were designed and synthesized. After PK15 cells were transected with siRNAs by Lipofectamine 2000, qRTPCR and 100 TCID50 were used to evaluate the level of αV expression and resistance of FMDV O/CHA/99, respectively. The results showed that compared with control and mock group, the αV subunit mRNA expression were obviously suppressed in all three experimental groups (iαV480, iαV1719 and iαV2077), especially the expression rate in iαV480 group was reduced by 90.1% in 24 hours. Lower virus titers of iαV480 group by TCID50 indicated that PK15 cells increased the resistance to FMDV O/CHA/99. The optimum siRNA toward porcine integrin αV subunit gene are successfully screened in this study, it would be helpful work about studying of interference FMDV receptor gene antiFMD transgene in swine.