At present, malignant tumors are one of the most important diseases that threaten human health, and related disability and fatality rates are increasing yearly. Protein disulfide isomerase A3 (PDIA3), an important member of the PDI family, is a type of mercaptan oxidoreductase with a wide range of functions. Its increased expression in a variety of tumors is closely related to the invasion and metastasis of tumor cells. Although numerous studies have shown that PDIA3 plays a crucial role in the occurrence and development of many tumors, the role of PIDA3 in digestive system tumors has not been systematically reported. Therefore, this paper reviews the different expression patterns of PDIA3 in four kinds of digestive system tumors and its clinical significance, and discusses its role in different stages of cancer development or clinical prognosis, so as to further search for effective early diagnosis and potential targets for gene therapy. It is of great significance to improve the survival rate of tumor patients.