<p>Cervical cancer (CC) remains one of the most prevalent malignancies among women worldwide. The role of long non-coding RNA (lncRNA) Cancer Susceptibility Candidate 2 (<i>CASC2</i>) is a tumor suppressor in various cancers. This study aims to explore the methylation status and expression levels of the <i>CASC2</i> gene in CC patients and correlate these findings with infection of human papillomavirus (HPV), risk factors, and sociodemographic and clinicopathological factors. This cross-sectional study was conducted on 81 CC patients and 36 control samples. Methylation-specific PCR (MS-PCR) and quantitative real-time PCR (qPCR) were performed to assess the promoter methylation status and expression level of <i>CASC2,</i> respectively. The GEPIA database was used to analyze the differential <i>CASC2</i> expression and survival status. Significant downregulation of <i>CASC2</i> expression was observed in CC cases, and the expression was associated with the methylation status of tumor samples (<i>p</i> &lt; 0.05). <i>CASC2</i> methylation status was observed to relate to the histological subtypes of CC as well as the degree of differentiation (<i>p</i> &lt; 0.00001). Moreover, HPV 16 &amp; 18 infections were considerably associated with socio-demographic factors like menopausal status, number of miscarriages/abortions and births, and first intercourse age. <i>CASC2</i> appears to perform a tumor suppressor in CC, which may be due to its promoter methylation. Further research with larger cohorts and comprehensive molecular analyses is necessary to validate <i>CASC2</i> as a diagnostic and prognostic biomarker and to explore its potential in targeted therapies.</p> Graphic abstract <p></p>