All in all, we firstly provide evidence that CRABP2 is strikingly downregulated in human ESCC, which is closely correlated with occurrence position, pathology, TNM stage, size, infiltration depth and cell differentiation of ESCC, and acts as a tumor suppressor both in vitro and in vivo, giving clues for further studies on the mechanisms of CRABP2 in esophageal tumorigenesis and providing a possible molecular candidate for predicting the development of EC. This evidence concerns the gene CRABP2 and neoplasm.