Abstract: A disease called " Shuibiezi” in Eriocheir sinensis was prevailed on Xinghua city, Jiangsu province since 2015, and slowly spread to other main areas of crab rearing in the whole nation. To explore the causes, the etiology by parasites examination, pathogenic bacteria isolation, challenge experiment and electron microscopy observation, and the histopathology by routine paraffin-section technique were conducted with healthy E. sinensis as control groups. Results showed that no pathogenic microorganism was detected by etiology research. Pathological changes with different degrees were observed in gills, muscles and hepatopancreas of diseased crabs, and the main pathological characteristics were gill tissue thickening, enlarged gill cavity, increased number of hemocyte, and marginalized nucleus. Vacuolization of the epithelial cells of the hepatopancreas and transferred vacuoles appeared. With the severity of the conditions, hepatic cells were irregular-arranged, and the number and volume of vacuoles and transferred vacuoles increased, and the number of granular materials in transferred vacuoles increased. With the most severe disease, the hepatic tubles were so ruptured that substances in cells were leaked, and the nucleus of hepatic cells were broken and hepatic cells appeared necrosis. The main lesion characteristics of muscle were muscular fibers appeared to be relaxed and pyknotic of nuclei. Etiology and incidence investigation revealed that the disease was caused by non living agents. Based on the main pathological characteristics and pathogenesis, this disease nominate scientifically as hepatopancreatic necrosis syndrome.