The etiological agent of cervical cancer is the infection with High- risk Human Papillomavirus. The oncoproteins E6 and E7 are responsible for the pathogenicity of this virus. The HR-HPV E6 protein binds to the tumor suppressor protein p53 via the E6AP ubiquitin ligase, inducing p53's ubiquitination and subsequent degradation by the proteasome. In this study, we investigate the association between TP53 rs1042522 polymorphism and the risk of cervical cancer among women in Tunisia and its potential role in the progression of cervical intraepithelial neoplasia. A total of hundred and eight cases including ninety-eight swabs and ten tissue samples were collected, between April 2023 and April 2024, from female participants addressed to the Pathology Department of the Pasteur Institute for HPV screening. Sequencing analysis identified three rs1042522 genotypes corresponding to wild (CC), and two mutant types, GG and CG. We found that women exhibiting mutant genotypes (CG and GG) had increased risk to cervical intraepithelial lesion progression. Interestingly, almost all patients diagnosed with cervical cancer had the mutated genotype. The association between TP53 rs1042522 and the development of cervical intraepithelial neoplasia was significant, P = 0.037; P < 0.05. Our results suggest this polymorphism as a potential biomarker linked to the progression of cervical precancerous lesions in the Tunisian women.