This review updates physicians on available biomarker tests for hepatocellular carcinoma (HCC) surveillance and follow-up. It provides an update on newly emerging tests and their diagnostic accuracy compared to standard protocols. The article aims to promote further investigation into high utility tests and continue the pursuit of clinical utility for emerging biomarkers such as circulating tumor DNA (ctDNA). Alpha-fetoprotein (AFP) is the traditional biomarker for HCC, but it has limitations. Other biomarkers such as AFP-L3 and des-gamma-carboxyprothrombin (DCP) have shown clinical utility but also limitations. Emerging biomarkers like ctDNA, genomic glycosylation, and non-invasive salivary metabolomics and microRNAs show promise for early detection and long-term surveillance but require large-scale validation. The review discusses the clinical use of biomarkers in early detection, post-transplant prognosis, and post-operative surveillance. It highlights the importance of combining biomarkers with imaging and AFP for improved diagnostic accuracy. Emerging biomarkers such as risk stratification SNPs, non-invasive saliva and breath markers, blood-based proteomics/metabolomics, genomic and cellular changes, and ctDNA show significant potential. However, most require further validation for clinical implementation. The study concludes that while AFP remains a key biomarker, emerging biomarkers offer greater potential for early detection and long-term follow-up. ctDNA, genomic glycosylation, and non-invasive salivary biomarkers are promising but need large-scale validation. The review emphasizes the need for further research and clinical trials to validate these emerging biomarkers for widespread use.This review updates physicians on available biomarker tests for hepatocellular carcinoma (HCC) surveillance and follow-up. It provides an update on newly emerging tests and their diagnostic accuracy compared to standard protocols. The article aims to promote further investigation into high utility tests and continue the pursuit of clinical utility for emerging biomarkers such as circulating tumor DNA (ctDNA). Alpha-fetoprotein (AFP) is the traditional biomarker for HCC, but it has limitations. Other biomarkers such as AFP-L3 and des-gamma-carboxyprothrombin (DCP) have shown clinical utility but also limitations. Emerging biomarkers like ctDNA, genomic glycosylation, and non-invasive salivary metabolomics and microRNAs show promise for early detection and long-term surveillance but require large-scale validation. The review discusses the clinical use of biomarkers in early detection, post-transplant prognosis, and post-operative surveillance. It highlights the importance of combining biomarkers with imaging and AFP for improved diagnostic accuracy. Emerging biomarkers such as risk stratification SNPs, non-invasive saliva and breath markers, blood-based proteomics/metabolomics, genomic and cellular changes, and ctDNA show significant potential. However, most require further validation for clinical implementation. The study concludes that while AFP remains a key biomarker, emerging biomarkers offer greater potential for early detection and long-term follow-up. ctDNA, genomic glycosylation, and non-invasive salivary biomarkers are promising but need large-scale validation. The review emphasizes the need for further research and clinical trials to validate these emerging biomarkers for widespread use.