Cell-free DNA (cfDNA) liquid biopsy technology is widely applied in non-invasive prenatal testing (NIPT). Traditional NIPT approaches that only utilize single genetic markers frequently yield inaccurate and unstable testing results, particularly in clinical samples with lower fetal fetal fraction, which limits diagnostic reliability. CfDNA methylation serves as a vital epigenetic biomarker carrying specific fetal genetic information that complements the deficiencies of conventional single-modal detection. This study develops an optimized analytical framework centered on cfDNA methylation profiles to enhance the overall performance of non-invasive prenatal testing. We established a standardized data analysis workflow to precisely extract, calibrate and purify cfDNA methylation signals, eliminating biological noise and systematic detection errors that commonly affect prenatal screening. The integrated strategy dominated by methylation biomarkers significantly enhances the accuracy of fetal genetic assessment and effectively reduces false-positive outcomes in NIPT.