Abstract: Liver cancer is one of the most lethal cancer types world-wide with low early diagnosis, and the patient is usually in advanced stage when the disease is diagnosed. Early diagnosis is an important means to reduce the mortality of patients with liver cancer, but there is no reliable hematological molecular marker for the diagnosis of liver cancer. Circulating free DNA (cfDNA) methylation detection is a potential non-invasive method for tumor diagnosis. Combined with the recent studies on circulating free DNA methylation in the diagnosis of liver cancer, this paper mainly reviewed the research progress of single DNA methylation markers in blood, the combination of multiple DNA methylation markers, and the combination of DNA methylation markers with alpha-fetoprotein (AFP) in the diagnosis of liver cancer.