Objective To explore the risk factors of esophageal cancer and these factors' interaction Methods 472 new diagnosed cases of esophageal cancer in 2004—2005 and 472 controls were investigated by case-control study. Etiological fractions and interactions between family history of esophageal cancer and other risk factors of esophageal cancer were analyzed. Results The significant independent risk factors included taking hot-meal, preferring pickled-vegetables, preferring dry-rigidity-food, being irritable, drinking polluted-water perennially, family history of esophageal cancer and drinking alcohol a great deal. The etiologic fractions attributable to interaction were 0.855, 0.758, 0.683, 0.464, 0.459, 0.343 and 0.108 respectively. The synergy indexes of family history of esophageal cancer with taking hot-meal and with preferring dry-rigidity-food were both 0.86. Concludes The interactions between family history of esophageal cancer and ill life-behavior-style or drinking polluted-water perennially were particularly significant in the development of esophageal cancer in Dongping County.