Hepatocellular carcinoma (HCC) is responsible for approximately 600,000-700,000 deaths worldwide. It is highly prevalent in the Asia-Pacific region and Africa, and is increasing in Western countries. Alpha fetoprotein (AFP) alone is insufficient for HCC screening. A combination with other tumor markers, such as PIVKA-II and AFP-L3, and periodical ultrasound surveillance is necessary. Sensitivity of AFP in depicting HCC is highest, followed by PIVKA-II and AFP-L3, but the order of the specificity is inverse, AFP-L3, PIVKA-II, and AFP. Sonazoid-enhanced ultrasound (US) is extremely useful to characterize hepatic tumors equal to or more than multidetector row computed tomography (MDCT). Sonazoid-enhanced US with defect re-perfusion imaging is a breakthrough technique in the treatment of HCC. Defect re-perfusion imaging will markedly change the therapeutic strategy for liver cancer. Gd-EOB-DTPA-magnetic resonance imaging is a newly developed imaging technique in the detection and diagnosis of HCC. It is the most sensitive tool in the differentiation of early HCC from dysplastic nodules. Regarding the treatment strategy, there has been no established systemic chemotherapy for advanced HCC, except for Sorafenib. Empirically, intrahepatic arterial infusion chemotherapy using implanted reservoir port is known to be effective in response rate and overall survival for advanced HCC with vascular invasion. Sorafenib in combination with transcatheter arterial chemoembolization or adjuvant use after ablation or resection will significantly prolong the life expectancy if ongoing clinical trials provide positive results. In conclusion, it is expected that readers will gain deeper insight into the latest progress and updated diagnosis and treatment of HCC described in this review.