Background <p>The triage of Atypical Squamous Cells (ASC) is pivotal in cervical cancer (CC) screening. This study aimed to evaluate the performance of paired box 1 gene methylation (<i>PAX1</i>^<i>m</i>) testing for triaging cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) in an ASC population and to compare it with high-risk human papillomavirus (hrHPV) testing.</p> Methods <p>This retrospective study was conducted from June 2023 to October 2025 and analyzed 1,305 women with ASC. Residual cervical cell samples were used for <i>PAX1</i>^<i>m</i> testing, and their hrHPV test results within two months were collected for comparison. All participants underwent colposcopy-biopsy to obtain the histopathological results. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity of the two methods was calculated and compared.</p> Results PAX1^<i>m</i> <p>difference of cross points (ΔCp) values showed a negative correlation with lesion severity (<i>P</i> _trend &lt;0.001). For CIN3 + detection, <i>PAX1</i>^<i>m</i> (cut-off: ΔCp ≤ 11.74) demonstrated comparable sensitivity to hrHPV (94.6% vs. 94.6%), but with significantly higher specificity (66.0% vs. 10.4%, <i>P</i> &lt; 0.001). Its AUC was also significantly higher to that of the hrHPV test. For CIN2 + detection, the AUC of <i>PAX1</i>^<i>m</i> (cut-off: ΔCp ≤ 11.74) was 0.716, which was significantly higher than that of the hrHPV test (0.544, <i>P</i> &lt; 0.001). Furthermore, <i>PAX1</i>^<i>m</i> detected all cases of CC.</p> Conclusion <p>In the triage of ASC, <i>PAX1</i>^<i>m</i> significantly improved the specificity for detecting CIN3 + while maintaining high sensitivity. These findings suggest that <i>PAX1</i>^<i>m</i> is a promising triage strategy with diagnostic performance superior to that of hrHPV, warranting further prospective validation of its clinical impact and cost-effectiveness.</p>