Although Human Papillomavirus is an unquestionable etiological factor for Cervical carcinoma but additional genetic and immunological factors are required to fuel the carcinogenesis. HLA-E is a unique, non - classical HLA class 1 molecule which modulates both innate and adaptive immunity via interaction with natural killer (NK) cells and T cell receptors. HLA-E interacts with CD94/NKG2A receptors on NK cells and prevents NK cell mediated lysis and contributes to the immune escape of the tumor cells and virus infected cells. The current study analyses the HLA-E protein expression in HPV infected cervix and cervical carcinoma tissue. Fresh tissue was obtained from Cervical squamous cell carcinoma patients and normal tissue from patients undergoing hysterectomy. Extracted DNA was subjected to Human Papillomavirus (HPV) genotyping using dot blot hybridization platform. Western blotting was performed on the tissue lysates. The protein intensity data was acquired using the image software and normalized with internal control GAPDH. In addition, peripheral blood samples were collected as well and subjected to ELISA to determine the serum HLA-E levels. Tissue samples were available in 32 cases of carcinoma cervix and 43 cases of clinically normal cervix. The high-risk HPV was observed in the entire cohort of carcinoma cervix and the subtypes observed were HPV 16 alone in 31(72%) and rest 12 cases had multiple subtypes. The protein expression of HLA-E was studied in HPV infected normal cervical tissue, normal cervical tissue (HPV negative) and carcinoma cervix. The HLA-E expression was significantly increased in cervical cancer tissue as compared to normal cervical tissue (p=0.000) and was nearly significantly increased in HPV infected cervix (p=0.057). The blood samples were available for 43 cases of carcinoma cervix and 55 cases of normal cervix. The soluble HLA-E levels were significantly increased in carcinoma cervix as compared to normal cervix group (P= 0.038). All the above findings uphold the hypothesis that upregulation of HLA-E protein expression in the microenvironment plausibly play role in progression to cervical carcinoma by facilitating the persistence and maintenance of HPV infected cells and immune escape of the tumor cells in the host.