Background: Viruses may play a role in the development of esophageal cancer (EC), although this is not yet known with certainty. This study, which examines Sudanese individuals with esophageal tumors, seeks to identify the involvement of cytomegalovirus (CMV) and herpes simplex virus (HSV) in the development of esophageal cancer. Materials and methods: This study looked back at 61 blocks of formalin-fixed, paraffin-embedded (FFPE) tissue that had already been identified as esophageal cancers. It used immunohistochemical staining to find herpes simplex virus type 1 and cytomegalovirus. Data were obtained from histopathology laboratories at the National Health Laboratory (NHL) and Soba University Hospital between January 2017 and January 2020. Positive results were confirmed with the polymerase chain reaction (PCR) technique. Results: Of the 61 FFPE blocks analyzed, 35 (57.4%) belonged to men. The bulk of participants (54.1%) were older than 60 years old. The most prevalent tumor type was squamous cell carcinoma (SCC), which accounted for 75.4% of cases. 16.4% of participants, equally divided between males and females, tested positive for HSV. 70% of HSV positive results came from people over the age of 60, and all of them were in SCC cases. Males accounted for 57% of the positive results. Individuals over the age of 60 were responsible for 80% of positive CMV results, while SCC cases accounted for 85%. All the PCR results were negative. Conclusion: These results imply a link between HSV, CMV, and esophageal cancer. We need more research with a larger sample size to understand how these viruses cause esophageal cancer.