Gastroesophageal reflux disease (GERD) is caused by recurrent exposure of the esophagus, oropharynx or lungs to acidic and nonacidic refluxate of gastric contents from the stomach, which causes discomfort or complication. It is characterized by recurrent attacks and difficulty to cure. The pathogenesis of GERD has not been fully elucidated at present, especially the causes of atypical symptoms and related mechanisms. Among them, the important role of esophageal mucosal immunity and inflammation in the pathophysiological mechanism of GERD has always been the focus of researchers. As a kind of common immune cells, mast cells exist widely in the human digestive tract, which can make short-term or long-term effects on gastrointestinal tract through proliferation, infiltration, activated degranulation and release mediator. Especially for GERD, irritable bowel syndrome and inflammatory bowel disease, mast cells play an important role in the pathophysiological mechanism. This paper reviews the complex pathophysiology in GERD, which will enhance our understanding to GERD and its complications, providing new treatment insights.