Interferon (IFN) is used in the treatment of many malignancies and viral disorders. We recently reported a significant correlation between the efficacy of IFN-alpha combined with chemotherapy in the treatment of advanced hepatocellular carcinoma (HCC) and IFN-alpha/type I IFN receptor (IFNAR2) expression. It is possible that the expression of IFNAR2 in gastrointestinal cancerous tissue, apart from HCC, may predict the efficacy of IFN-alpha combination therapy. We investigated the expression of IFNAR2 in 100 gastrointestinal cancerous tissues. IFNAR2 expression was examined using immunohistochemistry, in surgically resected tissue samples (20 esophageal, 20 gastric, 20 colorectal, 20 cholangiocarcinoma, and 20 pancreatic samples). The expression rate of IFNAR2 was 35.0% (7/20), 25.0% (5/20), 20.0% (4/20), 45.0% (9/20), and 25.0% (5/20) in esophageal, gastric cancer, colorectal, cholangiocarcinoma and pancreatic cancer samples, respectively. In our previous report, the expression rate of IFNAR2 in HCC samples was 64.8% (59/91). Thus, the expression rates of IFNAR2 in the five types of gastrointestinal cancers tested here were low, compared with HCC. The clinical efficacy of IFN-alpha mono- or combination therapies in patients with gastrointestinal neoplasms is expected to be lower than in patients with HCC based on the expression level of IFNAR2.