Background and Aims: The caspases are unique proteases that mediate the host cell apoptosis during viral infection. In this study, we identified the caspase cleavage motifs of H5N1 and H9N2 influenza viruses isolated during 1998-2012. Materials and Methods: Amino acid sequences of the eleven proteins encoded by the viruses as the caspase substrates downloaded from NCBI. The caspase cleavage motifs predicted at the three scanning P4P1, P4P2', and P14P10'–trained support vector machine classifier. Results: Data showed that H5N1 and H9N2 viruses were represented the same cleavage motif pattern for some of the viral proteins substrates. The HA, NP, and NS1 of H9N2 viruses were found to possess additional cleavage motifs from 2005, when an outbreak wave of H5N1 viruses was expanded through Asia. Conclusion: Moreover, the cleavage motif of PB1-F2 protein was differing in both subtypes. The results indicated that the caspase activity of PB1-F2 protein may be involve in the viral pathogenicity.