Abstract: The present study cloned and sequenced Hyriopsis cumingii PGRPS3 (hcPGRPS3) and measured its expreesion in multiple tissues. Results showed that the hcPGRPS3 cDNA sequence was 1438 bp in length, consisting of a 858 bp open reading frame (ORF) encoding 285 amino acid residues with 32.3 ku of predicted molecular weight and 7.98 of the theoretical isoelectric point, which have no signal petptide and transmembrane helices but have two latent N-glycosylation sites N40PT and N92YS. Multiple alignment analysis revealed that hcPGRPS3 shareed the highest identity with Euprymna scolopes PGRP4 (51%). hcPGRPS3 expressed in all examined organs of healthy H. cumingii with the low level in gill, heart and mantle and high level in gonad and hepatopancreas. Lipopolysaccharide and Peptidoglycan obviously up-regulated the expression of hcPGRPS3 in hepatopancreas, suggesting that hcPGRPS3 may play an important role in H. cumingii hepatopancreas innate immunity system against bacterial challenged.