Human papilloma virus (HPV) related cervical cancer (CC) remains a significant cause of mortality, especially in developing nations. Practical, cheap, and responsive biomarkers are required to diagnose and prevent large-scale CCs and other cancers associated with HPV. This research aimed to investigate HPV-Human leukocyte Antigen-G (HLA-G) interaction with the cervical cancer immune modulation: Hypothesizing HPV-specific HLA markers might be accurate and cost-effective preventive biomarkers. In addition to assessing the host immune response by immunophenotyping of CD57 natural killer T-cells. Forty-five DNA and serum samples of the patients were divided into two groups; twenty-three cases with HPV infection associated with cervical cancer and twenty-two controls with HPV infection without cervical cancer. Real-Time Quantitative polymerase chain reaction (RT-PCR) was used for HLA-G messenger RNA expression. Immunophenotyping by flow cytometry was carried out using specific monoclonal antibodies against CD57 expressed on CD8+ T-cells. The results indicated that 69.6% of the cases showed HLA-G expression compared to only 22.7% of the controls, and the difference was statistically significant at p < 0.01. Cases have eight times the risk of expression among controls since odd ratio (OR) =7.8. Also, 65.2% of the cases showed CD57⁺ expression compared to 36.4% of the controls, and the difference was marginally significantly different at p= 0.053. Cases have nearly three times the risk of expression among controls since OR=3.3. Although the lower limit of the 95% confidence interval is <1, indicating that in the population, this increase in risk may not be present. HPV-specific HLA-G marker test might be an accurate and cost-effective preventive biomarker with potential application for cervical cancer.