Introduction: Esophageal squamous cell carcinoma is among the leading causes of cancer related deaths within gastrointestinal tumors. There is a growing body of evidence that shows an association between Epstein Barr virus infection and the development of malignancies such as B-cell non-Hodgkin’s lymphoma, Hodgkin’s disease, and Burkett’s lymphoma. However its potential association with esophageal squamous cell carcinoma is controversial. Therefore, in the present study, we have explored the association of Epstein Barr virus with pathological information and clinical outcomes of 108 esophageal squamous cell carcinoma patients.Methods: There were 48% female and 52% male patients with a mean age of 59.2±11.1 years who enrolled in this study. Patients had the following tumor stages: T1 (5.6%), T2 (21.3%), and T3 (71.3%). A total of 32.4% had lymph node metastases. In order to explore whether patient characteristics might influence clinical outcome, we analyzed data on progression-free survival and overall survival according to patients’ clinicopathologic features.Results: An association existed between tumor size, node and metastasis status, and stage with shorter overall and progression-free survival. We observed that 6.5% of patients had Epstein Barr virus. All patients infected with Epstein Barr virus had T2 and T3 disease.Conclusion: Our findings demonstrated the presence of Epstein Barr virus in 6.5% of Iranian patients and its potential link with tumor size. Additional studies in multicenter settings should be conducted to determine the association of Epstein Barr virus with development and progression of esophageal squamous cell carcinoma.