This study aimed to investigate the role of high-risk human papillomavirus (Hr-HPV) in Somalian and Turkish patients with esophageal squamous cell carcinoma (ESCC). In the sections obtained from paraffin-embedded blocks, the results of invasive tumor, peripheral tumor dysplasia and normal mucosa were examined. Samples containing 45 and 47 ESCC, 46 and 42 dysplasia in Somalian (n = 52) and Turkish (n = 53) cases, respectively, were included in the study. We examined the presence of 14 types of Hr-HPV in ESCC collected from Somalia and Turkey by Aptima® Panther System. Hr-HPV types were not detected in Somalian cases. p16INK4a is positive in 5 (11.4%) tumors and 6 (13%) dysplasia. p53 is positive in 28 (62.2%) tumors and 35 (76.1%) dysplasia. HPV16-18/45 are positive only in one of the Turkish cases. p16INK4a is positive in 5 (10.6%) tumors and 4 (9.5%) dysplasia. p53 is positive in 31 (63.3%) tumors and 24 (57.1%) dysplasia. No reaction was detected in normal mucosa samples in both countries. This study is regional. Although the findings did not reflect the general population, the present study shows that the effect of HPV on carcinogenesis in Somalian and Turkish ESCC patients was not significant.