Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associatedmorbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis ofHCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin(DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2(TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), andsquamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC.The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US),dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some expertsadvocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced USas the promising imaging madalities of choice. With regard to recent advancements in tissue markers, manycuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostainingstudies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less thanhalf of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation,surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard ofcare with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads andradioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years,several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currentlythe only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCCpatients with well-preserved liver function who are not candidates for potentially curative treatments, suchas surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus(HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis Bvirus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is notyet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC,although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still areasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors,including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolongedaflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects againstHCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatmenthas proven to be a rational strategy.