S100A14 is one of the multifunctional S100 protein family members, which is involved in a wide range of biological functions, such as cell proliferation, differentiation and apoptosis, invasion and metastasis. Its expression presents cell and tissue specificity in a variety of tumors, and its expression level is related to the prognosis of patients. In digestive system tumors, S100A14 exerts its function mainly through binding to the target protein, but the action mechanism has not been fully elucidated. Here, the authors review the molecular structure and function of S100A14, and its expression and action mechanism in the digestive system tumors.