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Liquid biopsy of cell-free DNA (cfDNA) has attracted much attention for its promise to realize pan-cancer detection in a non-invasive way. The whole-genome bisulfite sequencing (WGBS) is widely used in cfDNA sequencing analysis and lays the foundation for further study on cfDNA. The cfDNA released by multiple tissues carries genetic and epigenetic information. Methylation patterns, copy number variation (CNV) and fragmentation changes have been discovered in previous studies and achieved a promising accuracy. In this review, different cancer detection methods based on these three biomarkers are introduced. In addition, feature fusion is discussed for its potential in enhancing performance in clinical applications.