Zinc finger proteins (ZNFs) belong to the largest transcriptional factor family in human genome. ZNFs are widely involved in the development and progression of digestive system cancers by promoting or inhibiting carcinogenesis. Studies have shown that the abnormal expressions of various ZNFs are closely related to the clinicopathologic features and prognosis of patients with digestive system cancers, including gastric cancer, liver cancer, colorectal cancer and pancreatic cancer. Exploring the underlying mechanism of ZNFs will help to provide new targets for clinical treatment of digestive system cancers.