Epidermodysplasia verruciformis (EV) is a genodermatosis related to human beta-papillomavirus (beta-HPV), with a high risk of cutaneous squamous cell carcinoma (cSCC). Claudins are transmembrane proteins expressed in epithelia and may be altered during carcinogenesis. For a better understanding of the role of beta-HPV in cutaneous carcinogenesis, this claudin expression study was conducted on lesions of patients with and without EV. In this study, claudins-1, -2, -3, -4, -5, -7 and -11 expressions were analyzed by applying the immunohistochemistry technique, in samples of 108 normal skin, 39 flat warts and 174 cSCC. The cSCC samples were organized in tissue microarrays. We found that claudin-1 and claudin-3 focal expressions were associated with cSCC (p < 0.001), and claudin-2 focal or negative expression with flat wart (p < 0.001), in EV and NEV (non-EV) groups. For claudin-5, EV group showed a lower chance of focal and negative expression (p < 0.001), and its negative expression was associated with flat wart (p < 0.001) and lower mean age (p < 0.001). Claudins-4, -7 and -11 showed a diffuse expression in almost all studied samples. Our findings suggest that claudin-5 increased expression observed on normal skin, flat wart and cSCC showed association with EV. Claudin-1 and -3 down expression were also observed, but they could not be related to beta-HPV infection.