Abstract: Cell Division Cycle 42 protein (CDC42) is a member of Rho family GTPases and plays an irreplaceable role in innate immunity such as phagocytosis and inflammation. In this study, the full-length cDNA of Penaeus monodon CDC42 (PmCDC42) was cloned and characterized. The full-length PmCDC42 cDNA consisted of 2 233 bp with a 576 bp open reading frame, encoding 191 amino acids. The quantitative real-time PCR (qRT-PCR) analysis shows that PmCDC42 was ubiquitously expressed in all tested tissues and the highest expression level was obtained in the hemolymph. The expression pattern of PmCDC42 in the gill and hepatopancreas was detected under different conditions such as pH challenge, salinity stress, heavy metal cadmium exposure and Vibrio harveyi challenge. The results show that the expression levels of PmCDC42 mRNA in hepatopancreas and gill were up-regulated after different environmental stress, especially V.harveyi challenge. The results indicate that PmCDC42 may play an important role in immunity of P.monodon.