Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world, and the third most common cause of cancer-related death. It affects mainly patients with cirrhosis of any etiology. Patients with cirrhosis are thus usually included in surveillance plans aiming to achieve early detection and effective treatment. Only patients who would be treated if diagnosed with HCC should undergo surveillance, which is based on ultrasonography and alpha-fetoprotein every 6 months. Upon diagnosis, the patients have to be staged to define tumor extent and liver function impairment. Thereafter, the best treatment option can be indicated and a prognosis estimate can be established. The present manuscript depicts the Barcelona-Clínic Liver Cancer Group diagnostic and treatment strategy. This is based on the analysis of several cohort and randomized controlled studies that have allowed the continuous refinement of treatment indication and application. Surgical resection is considered the first treatment option for early stage patients. It is reserved for patients with solitary tumors without portal hypertension and normal bilirubin. If these conditions are not met, patients are considered for liver transplantation (cadaveric or live donation) or percutaneous ablation if at an early stage (solitary < or =5 cm or up to 3 nodules < or =3 cm). These patients will reach a 5-year survival between 50 and 75%. If patients are diagnosed at an intermediate stage and are still asymptomatic and have preserved liver function, they may benefit from chemoembolization. Their 3-year survival will exceed 50%. There is no effective treatment for patients with advanced disease and thus, in such instances, the patients have to be considered for research trials with new therapeutic options. Finally, patients with end-stage disease should receive only palliative treatment to avoid unnecessary suffering.