The plasminogen activator inhibitor type-2 (PAI-2) dependent apoptosis protection is due to the 33 amino acids fragment located between helix C and D of PAI-2, this fragment may interact with some unknown intracellular proteins. In this study we used the fragment between helix C and D of PAI-2 as a bait to perform a yeast two-hybrid screen using a cDNA library constructed with HeLa cells during apoptosis,and retrieved a clone encoding 94 amino acid residues of C-terminus of pre-mRNA processing factor 8(PRPF8). Co-immunoprecipitation experiments confirmed that PAI-2 could interact with PRPF8 in vivo.PAI-2 could bind PRPF8 C-terminal in both the inside and outside of nuclear. These results suggested that the interaction between these two proteins might not be involved in the apoptosis process.