Changes in ammonia content over the years due to agricultural activities and anthropogenic factors have had serious effects on aquatic organisms, especially the metabolism, immunity, molting, growth, etc. of crustaceans. In this study, we revealed that under high ammonia stress (HAS) conditions, decreased levels of oxyhemocyanin (OxyHMC) in Penaeus vannamei are due to the degradation of hemocyanin (HMC) into fragments. When P. vannamei were subjected to HAS for 12 h, 24 HMC fragments were identified as HMC derived peptides, one of which, designated HMCs27, with 366 bp in length, and encodes 122 amino acids was further explored. Injection of shrimp with recombinant HMCs27 (rGST-HMCs27, about 40 kDa) followed by HAS treatment significantly improved shrimp survival compared with control (GST).