According to statistical data, hepatocellular carcinoma (HCC) is one of the most malignant cancers with high incidence and mortality rates, causing a severe burden on society. In response to the serious situation of HCC, the search for efficient early screening methods has become a research hotspot both domestically and internationally. This article reviews the main serum markers for HCC over the past five years, including alpha-fetoprotein (AFP), alpha-fetoprotein-L3 isoform ratio (AFP-L3%), des-gamma-carboxy prothrombin (DCP), and Golgi protein 73 (GP73). It summarizes the advantages and limitations of these biomarkers and their role in combination with other indicators in the early screening of HCC, as well as the research progress. The article also proposes future development directions to assist in the diagnosis of HCC.