Mud crab Scylla paramamosains is widely cultured in brackish and seawater ponds along the coast of southeast China including Shantou. In recent years, mud crab cultured in Niutianyang reclaiming coastal area of Shantou suffered from serious diseases, especially the bacterial diseases (such as Vibrio parahaemolyticus), which results in high mortality and great economic loss. In present study, V.parahaemolyticus isolated from Shantou Niutianyang crab culture area was injected to S.paramamosains to study the differential gene expression of the mud crab by cDNA-AFLP technology. Furthermore, 20 fragments that exhibited differential expression were discovered and sequenced. The results show that 6 fragments are homologous to the known functional genes, 5 of which are up-regulated. They are involved in energy metabolism including arginine kinase, phosphoenolpyruvate-carboxykinase and glyceraldehydes 3 phosphate dehydrogenase, arginyl-tRNA synthetase involved in transport progress, as well as the chymotrypsin-like proteinase involved in defense response. The other 8 fragments were identified to be unknown function genes. The result here shows that the response of S.paramamosain upon V. parahaemolyticus infection is involved in multiple pathways and needs further investigation.