Acidification of seawater due to anthropogenic CO2, called as ocean acidification (OA), makes most coastal environments unfavorable for oysters. This is a serious socio-economical issue for China which is accounting for >70% of the world’s edible oyster supply. Understanding of OA effects at proteome level could lead to a better aquaculture management. Here, we present an iTRAQ based protein profiling analysis for the detection and quantification of proteome change under OA in one of the early life stages of a commercially important oyster species, Crassostrea hongkongensis. The completion of the genome sequence for oysters enabled us to confidently quantify over 1500 proteins in the larval oyster. Over 10% of proteome was altered in response to OA process at pH 7.6. Analysis of differentially expressed proteins and their associated pathways indicated that up-regulation of calcification, metabolic processes, cytoskeletal functions, oxidative stress and cell signaling processes might have been used by larvae to acclimate under OA. Although the expressions of cytoskeletal and signal transduction proteins were down-regulated in response to OA, there was no marked alternation in developmental processes such as metamorphic success. This study suggests that the estuarine edible oyster possess an adequate short-term adaptability or acclimation mechanism at proteome level to tolerate near-future OA scenario.