Ammonia stress is one of the most common, detrimental toxicants in the aquaculture environment. Procambarus clarkii, is an important aquaculture species that has high production and economic values in China. This study performed transcriptomic analysis of hepatopancreas from P. clarkii treated with ammonia-stress to investigate the effects of ammonia exposure on apoptosis, oxidative stress, and immune response. A total of 3,956 differentially expressed genes (2,562 up-regulated and 1,394 down-regulated genes) were identified in the ammonia stress group. Then, the genes (i.e., C type lectin, cathepsin, chitinase, and cytochrome P450) and pathways (i.e., autophagy, amino sugar and nucleotide sugar metabolism pathway, and AMPK pathway) related to immune were found to be significantly up-regulated, which confirmed that P. clarkii may promote immune defense to counteract ammonia toxicity. Our results will be helpful to understand the mechanism of aquatic toxicology induced by ammonia in P. clarkii. Highlights : 1. In this research, we demonstrated the effects of ammonia exposure on immune response, oxidative stress and apoptosis in Procambarus clarkii. 2. Procambarus clarkii can strengthen immune defense to cope with ammonia stress by upregulating immune-related genes and pathways. 3. Although procambarus clarkii had immune defense to cope with ammonia stress, high concentrations of ammonia still had immune damage to procambarus clarkii. [ABSTRACT FROM AUTHOR]