White hepatopancreas is a syndrome that has recently emerged in aquaculture of Chinese mitten crab (Eriocheir sinensis). High lethality of the disease caused large economic loss, which drew considerable attention of fish farmers and scientific researchers. In this study, hepatopancreas reference transcriptome was de novo assembled and differential expression analysis was conducted between white hepatopancreas and normal (yellow) hepatopancreas of E. sinensis. A total of 90,687 transcripts were assembled, and 27,387 were annotated. Transcriptomic comparison revealed 69 differentially expressed genes between individuals featuring white hepatopancreas and yellow hepatopancreas. Genes associated with immune response and cell death, include thioredoxin-related transmembrane protein 1, hemocytin, methuselah-like 1, and E3 ubiquitin-protein ligase, and they were up-regulated, whereas titin and 5-formyltetrahydrofolate cyclo-ligase, which are genes related to cell proliferation, were down-regulated in E. sinensis with white hepatopancreas syndrome. Our study provides novel insights into genetic causes of formation and novel gene markers for detection of white hepatopancreas syndrome in aquaculture of E. sinensis.