Hemocyanin, the respiratory protein of arthropods and mollusks, was found to function against bacterial and fungal invasion. In this study, we show that this protein complex could delay the infection of white spot syndrome virus (WSSV) in vivo and cloned two hemocyanin subunits genes (PjHcL and PjHcY) from the shrimp Penaeus japonicus. Further investigation of their transcriptional regulation during viral invasion showed that in contrast to subunit PjHcY, PjHcL expression could be strongly induced by WSSV infection. These findings not only reveal an important role of hemocyanin in shrimp antiviral defense but also suggest a possible discrepancy between the two subunits in shrimp innate immunity.