In an attempt to get insight into the biological functions of p93 in the cardiovascular system and its potential roles in the signaling pathway, a yeast two-hybrid technology was carried out to screen the adult heart cDNA library using the N-terminal fragment of p93 (101～372 aa) as bait. Peroxiredoxin 3 (PRX 3) was identified as a novel p93 binding protein. Subsequently, the interaction was confirmed by in vitro binding assay and co-immunoprecipitation and p93 was showed to co-localize in part with PRX 3 in HEK-293FT cells by immuofluorescence. Taken together, these observations suggest that p93 may participate in various pathophysiologic processes mediated by PRX3 in cardiomyocyte, such as cell growth, differentiation, development，apoptosis and oxygen stress.