Hypoxia inducible factor‐1α(HIF‐1α)and histone deacetylase(HDAC)expressions in gastrointestinal cancer, especially intrahepatic cholangiocarcinoma and pancreas cancer, significantly reflect on the malignant potential of these cancers, and are significantly associated with patient’s prognosis. It has also been shown that HIF‐1α is deacetylated and stabilized by nucleosome remodeling and histone deacetylation (NuRD) complex, consisting of HDAC and metastasis-associated gene‐1(MTA1), leading to angiogenesis. More recently, it has been reported that HIF‐1α induces tumorigenesis and ultimately cancer stemness through epithelial-mesenchymal transition (EMT). Therefore, HIF‐1α may be one of the master molecules of cancer progression, and it is expected that novel therapeutic strategies will be devised by controlling the signaling pathway of HIF‐1α in hypoxic condition of gastrointestinal cancer