Oncoprotein NM23, as a family of genes encoding the nucleoside diphosphate (NDP) kinase, plays important roles in bioenergetics, DNA replication, differentiation and tumor metastasis. In this study, a full-length cDNA of NM23 (designated EcNM23) was cloned from Exopalaemon carinicauda by using rapid amplification of cDNA ends (RACE) approaches. The full-length cDNA of EcNM23 was 755 bp, which contains an open reading frame (ORF) of 518 bp, encoding a 175 amino-acid polypeptide with the predicted molecular weight of 19.60 kDa and estimated isoelectric point of 7.67. The deduced amino acid sequence of EcNM23 shared high identity (86%–93%) with that of other crustaceans. a NDP kinase super family signature was identified in E. carinicauda EcNM23. Quantitative real-time RT-qPCR analysis indicated that EcNM23 was expressed in all the examined tissues with the high expression level in hemocytes and ovary. The EcNM23 expression in immune-related tissues changed rapidly and reached peak at different time after pathogens (Vibrio parahaemolyticus and WSSV) challenge and ammonia-N stress treatment. The results suggested that EcNM23 might be associated with the immune defenses to pathogens infection and ammonia-N stress in E. carinicauda.