Histidine triad nucleotide binding protein (HINT) represents the most ancient and widespread branches in the histidine triad superfamily. HINT plays an important role in many biological processes especially in cell biology, and it has been found in a wide variety of species. However, the functional attributes of HINT homologues in invertebrates have not yet been reported. Here we identified a HINT homologue in abalone, which we named ab-HINT. The ab-HINT shows significant structural and functional similarities to mammalian HINT. RT-PCR and western blot analysis show that ab-HINT is ubiquitously expressed in abalone tissues and highly expressed in hemocyte and gills. In addition, significant up-regulation of ab-HINT was observed after LPS or Poly I:C challenge. Immunostainings suggest that ab-HINT is expressed predominantly in epithelial cells and mainly localized in the cytoplasmic compartment. Studies of the effect on cell apoptosis indicate that ab-HINT can trigger hemocytes apoptosis and p53 is involved in this process. These results conclude that ab-HINT is involved in the immune response of abalone and may be a potential pro-apoptotic factor. To the best of our knowledge, this is the first identification and characterization of a HINT homologue in invertebrates.