Lower pH gives rise to a harmful stress to crustacean. Here, we analyzed the proteomic response of Fenneropenaeus chinensis from control pH (pH value 8.2) and low pH (pH value 6.5) - treated groups by employing absolute quantitation-based quantitative proteomic (iTRAQ) analysis. Among the identified proteins, a total of 76 proteins differed in their abundance levels, including 45 upregulated and 31 downregulated proteins. The up-regulation of proteins like citrate synthase, cytochrome c oxidase, V-type proton ATPase, glyceraldehyde-3-phosphate dehydrogenase and fructose 1,6-bisphosphate-aldolase as well as the enrichment of the DEPs in multiple metabolic processes and pathways illustrated that increased energy and substrates metabolism was essential for F. chinensis to counteract low pH stress. Ion transporting related proteins, such as Na+/K+/2Cl− cotransporter and calmodulin, participated in the homeostatic maintenance of pH in F. chinensis. There were significant downregulation expressions of lectin, lipopolysaccharide- and beta-1,3-glucan binding protein, chitinase, cathepsin L and beta-glucuronidase, which indicating the immune dysfunction of F. chinensis when exposure to low pH condition. These findings can extend our understanding on the defensive mechanisms of the low pH stress and accelerate the breeding process of low pH tolerance in F. chinensis.