Nervous necrosis virus (NNV) has caused significant economic losses in Korea's aquafarms due to mass mortality in sevenband groupers during the summer season. However, the mechanisms of NNV infection are not well understood. To investigate these mechanisms and search for antiviral proteins, we have established a differentially expressed genes (DEGs) from naive sevenband grouper and NNV-infected ones. Among the highly expressed proteins was Cathepsin H, a lysosomal cysteine proteinase that plays a role in lysosomal protein breakdown. The open reading frame (ORF) of Cathepsin H (SG.CH) was 987 nucleotides long that codes for a protein of 328 amino acids (approximately 20 kDa molecular weight). The gene showed a high degree of identity (98%) with the Cathpesin H from the giant grouper (Epinephelus lanceolatus). When the gene expression profile was analyzed in various tissues, the highest expression was found in the kidney. While following the NNV infection, the expression profile of the Cathepsin H gene displayed a significant upregulation in brain at 48 hours after infection. These experimental results can help understand the mechanism of NNV infection.