The association between clinical characteristics, prognosis, and the ABO blood group of esophageal squamous cell carcinoma (ESCC) is rarely discussed. The aims of the current study were to investigate the correlation of the ABO blood group with the clinicopathological characteristics in a consecutive cohort of patients with ESCC and to assess whether the ABO blood group was associated with prognosis. A total of 511 patients with locoregional ESCC who underwent curative treatment were retrospectively analyzed at a single institution between January 2007 and December 2008. The relationship between the ABO blood group and clinicopathological variables was assessed by chi-squared analysis. The Kaplan-Meier method was used to estimate the 5-year overall survival (OS). The Cox proportional hazards model was used in univariate and multivariate analyses of OS. There were no significant differences in the clinicopathological characteristics among patients with different ABO blood groups. The 5-year OS rates were 50.0 % for patients with blood type A, 45.4 % for type B, 50.8 % for type O, and 60.7 % for type AB. In a subgroup analysis of 321 patients who ever smoked, the B/O group had a poorer OS compared with the A/AB group (p = 0.0245). Multivariate analysis revealed an unfavorable and independent impact of the B/O group on patient survival with ESCC who ever smoked (p = 0.011). Findings suggest the B/O blood type as a predictor of mortality in ESCC patients who ever smoked. Future studies conducted prospectively are warranted to confirm this work and to better understand the underlying biological mechanisms.