Abstract: Obejective: To investigate the role of familial history in the development of esophageal squamous cell carci-noma. This article analyzed the clinicopathologic differences in onset age, prevalence of double primary malignancy, and long-term post-surgical survival between familial cases and sporadic cases. Methods:There were476 cases in the familial group and 1226 cases in the sporadic group. T-test was used to explore the difference in onset age between the two groups. Chi-square test was employed to examine the prevalence of double primary ESCC. The difference in long-trem sur-vival rate between the two groups was analyzed with Cox proportional Hazard model.Results: Compared with the sporadic cases, familial ESCC cases had earlier onset age ( 51.9 ± 8.2 versus 53.4 ± 8.0 years, P t-test=0.00), higher prevalence of dou-ble ESCC (2.73% versus1.22%, adjusted with TNM: X2 MH=4.029 , P=0.045 ) and lower survival (Pwald=0.04). Conclusion:Our findings suggest the existence of an inherited genetic alteration in the familial ESCC cases. The systemic clinicopathologic differences between familial and sporadic ESCC cases revealed that the genetic predisposition can affect the onset age, the number of primary carcinoma, and the prognosis.