Abstract: Esophageal cancer is a common malignant tumor of digestive tract. Remarkable regional difference is a prominent feature of the clinical epidemiology of esophageal cancer. They are mainly manifested in incidence rate, incidence type, onset age, and gene mutation. These differences may be related to dietary habits, lifestyle, and environmental factors. In recent years, research on the regional differences in esophageal cancer has gradually deepened. This article summarizes the differences in incidence rate, incidence type, gene mutations, epigenetics, risk factors, and prognosis of esophageal cancer in different regions, including Asia (China, India, Japan, and other countries), Europe, America (the United States), Africa, and other regions. Understanding these differences can help doctors and public health experts understand the risk factors and causes of esophageal cancer and further develop highly effective prevention and treatment strategies to reduce the occurrence and mortality rate of this malignancy.