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Prognosis estimation in patients with hepatocellular carcinoma (HCC) can provide information at diagnosis and can indicate therapy. Because cirrhosis underlies HCC in most individuals, their outcome is related to both entities, which determine the applicability and efficacy of therapy. Accordingly, prognostic modelling should consider tumor stage, liver function impairment, the patient's general condition, and treatment efficacy. We have developed a system that stratifies patients into four categories, simultaneously setting prognosis and guiding the therapy. Patients with HCC (single HCC ≤5 cm or three or fewer nodules ≤3 cm) benefit from curative/effective therapies (resection, transplantation, and percutaneous ablation), expert application of which provides a 50% to 75% 5-year survival. Those with more advanced disease present a heterogenous outcome. Patients who do not present with cancer-related symptoms and whose tumor has not invaded vascular vessels or disseminated outside the liver may reach 50% survival at 3 years, and they benefit from chemoembolization. Those who present with symptoms (pain, deterioration of physical condition) and/or an aggressive tumor pattern do not reach a 10% survival at 3 years, and there is no effective therapy for them. Finally, those with severe liver function or health status impairment constitute the end-stage category and cannot be expected to survive more than 1 year.