Purpose: Diet and inflammation have been suggested to be important risk factors for esophageal squamous cell cancer (ESCC). In this study, we examined the association between the dietary inflammatory index (DII) and ESCC in a case–control study conducted between 1992 and 1997 in Italy. Methods: This study included 304 ESCC cases and 743 controls hospitalized for acute non-neoplastic diseases. The DII was computed based on dietary intake assessed by a reproducible and valid 78-item food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) conditioned on age, sex, year of interview, and area of residence and adjusted for education, smoking, alcohol drinking, BMI, physical activity, and aspirin use. Energy adjustment was performed using the residual method. Results: Subjects with higher DII scores (i.e., with a more pro-inflammatory diet) had a higher risk of ESCC, with the DII being used as both a continuous variable (ORcontinuous 1.39, 95 % confidence interval, CI, 1.25–1.54; one-unit increase corresponding to ≈ 12 % of its range in the current study) and a categorical variable (ORquintile5vs1 2.46, 95 % CI 1.40–4.36; ptrend < 0.001). Conclusion: These results indicate that a pro-inflammatory diet is associated with a higher risk of ESCC, even after controlling for alcohol and tobacco exposure.