Digestive system tumors account for more than half of all malignant tumors in terms of incidence and mortality, and thus pose a serious threat to human health. Haptoglobin (Hp) is an acute-phase glycoprotein that is elevated in both plasma and tumor tissues in various clinical conditions, including different types of cancer, such as liver, gastric, colorectal, pancreatic, and gallbladder cancer. Numerous studies have indicated that Hp plays a significant role in the prognosis of cancer patients, highlighting its potential as a prognostic marker for gastrointestinal tumors, with important clinical applications. Despite its demonstrated crucial role in the development of various tumors, however, the specific mechanisms of Hp in gastrointestinal tumors remain controversial. This review considers the differential expression and clinical significance of Hp in the five major types of gastrointestinal tumors, to explore its role in different stages of cancer progression and prognosis. This review thus aims to provide reliable and accurate serum biomarkers for the screening, early diagnosis, treatment, and prognosis monitoring of gastrointestinal tumors,with important implications for predicting the survival and prognosis of cancer patients.