Recent analyses revealed that estrogen receptor? a and hedgehog signal pathway both play important roles in gastric adenocarcinoma. Estrogen receptor? a has been shown to be involved in the regulation of proliferation, differentiation and tumorigenesis of gastrointestinal tract epithelium. Hedgehog family which includes Sonic (Shh), Indian (Ihh) and Desert (Dhh) hedgehogs, is involved in the vast majority of cellular processes and is fundamentally important in regulating cell proliferation, tissue generation and cell differentiation in adenocarcinoma. Experimental and mechanistic findings indicate that down-regulation of expression ER can induce expression of Shh in ER positive cancer cell lines. In this review, we summarize the implications of cellular and molecular mechanisms of estrogen receptor? a and hedgehog signal pathway related to the biochemistry and cell biology in gastric adenocarcinoma.