The Hedgehog (Hh) signaling pathway plays a crucial role in the development of the gastrointestinal tract and maintenance of the physiologic function of the stomach. Aberrantly activated Hh signaling is implicated in carcinogenesis as well as maintenance of cancer stem cells. Hh signaling is often aberrantly activated and plays an important role in the inflammation and carcinogenesis of gastric epithelial cells. Abnormal HH signaling activation not only causes uncontrolled proliferation of tumor cells but also contributes to the establishment of an immunosuppressive TME by regulating macrophage and T cell-dependent immune responses as well as the expression of tumor-related inflammatory factors. HH signaling activation is associated with certain GID, including Pallister–Hall syndrome, gut mal rotation and gastric cancer. In GIC, the expression of SHH and IHH signaling pathway components and their target genes is upregulated. Specifically, the expression of GLI1 is usually correlated with the degree of malignancy of gastric cancer, especially with lymph node metastasis