Hepatocellular carcinoma (HCC) ranks third among the causes of cancer deaths globally. The most frequent causes are the hepatitis C virus (HCV), a combination of alcohol/HCV and metabolic syndrome (MS). The introduction of new pharmaceutical drugs that inhibit protease will bring a relative increase in the number of cases of HCC that are linked to the consumption of alcohol and MS. The latest development in the diagnostic sector is the total recognition of the contrast-enhanced ultrasound diagnostic algorithm. In the treatment sector we are moving on from the Barcelona criteria. With nodules up to 3 cm in size and with favorable anatomical and clinical conditions, the first treatment choice is percutaneous ablation. The first choice for nodules that are 3-5 cm in size is still hepatic resection (HR). For cases that fall completely within the Milan criteria with portal hypertension and compromised liver function the first treatment choice, in the total absence of any contraindications, is certainly LT. Intermediate forms of HCC are the most complicated as the stratification of patients is particularly relevant. TACE certainly no longer represents the only choice. HR is preferable where possible. According to the individual case and during down-staging, LT may be proposed. In some cases both locoregional ablative approaches and sorafenib can be used. In advanced cases with preserved function, the best treatment is still sorafenib. The treatment of HCC is complex because of the extreme anatomic-clinical variability of the cases. The key to a successful and effective approach is the creation of a true multi-disciplinary group in which the various players have the opportunity to express their own opinion. This is an indispensable prerequisite for a successful synthesis.