The purpose of the present paper was to investigate the significance of DEK protein expression in uterine cervical lesions and its relationship with HPV infection status. DEK protein expression was studied in 253 cervical lesions, including 30 non-neoplastic cervix with or without squamous metaplasia, 64 cervical intra-epithelial neoplasias (CIN; CIN-1, n = 28; CIN-2, n = 17; CIN-3, n = 19), 102 squamous cell carcinomas (SCC), 51 adenocarcinomas, and six adenosquamous cell carcinomas (adenoSCC) on immunohistochemistry. For comparison, HPV-positive and -negative cervical cancer cell lines were also included. The HPV screening was performed using TaKaRa polymerase chain reaction. On immunohistochemistry DEK was found to be negative in all 30 non-neoplastic cervical epithelia, but it was positive in 96.1% of SCC (98/102), 92.2% of adenocarcinomas (47/51), 100% of adenoSCC (6/6), 85.7% of CIN-1 (24/28), 94.1% of CIN-2 (16/17), and 89.5% of CIN-3 (17/19). There was no significant difference between HPV-positive and -negative cervical lesions. Also, strongly positive staining was observed in all aforementioned cervical cancer cell lines regardless of HPV infection, according to immunocytochemistry. In summary, DEK plays an important role in the carcinogenesis of cervical cancers, and can be helpful for early diagnosis, and is a potential therapeutic target.