OBJECTIVES: Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide imposing high hospitalizations and mortality rates and a relevant economic burden. Objective of the present analysis is to investigate treatment pathways and healthcare costs for intermediate and advanced HCC patients (Barcelona Clinic Liver Cancer Classification (BCLC) stage B and C). METHODS: Structured interviews with gastroenterologists and interventional radiologists were performed in four Italian centres experienced in HCC management. Information on disease stage, diagnostic procedures, treatments and healthcare resource consumption related to HCC were recorded. Direct healthcare costs associated with relevant treatments (sorafenib, Transarterial chemoembolization (TACE), transarterial radioembolization (TARE) systemic treatment) were evaluated. RESULTS: Between 2013 and 2014, 285 patients with HCC (mean age 66 years, 74% males) were treated in the 4 participating centres; of them, 80 were classified in the intermediate stage and 57 in the advanced stage. TACE was the most frequent first-line treatment in intermediate stage HCC (63%), followed by sorafenib (15%), radiofrequency ablation (14%) and TARE (1,3%). In the advanced stage of HCC the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%) and TARE (3,5%). The mean duration of treatment with sorafenib (a total of 137 patients) was 6.1 months; the average number of TACE and TARE sessions was 2.5 and 1.5 procedures/patient, respectively. The total costs of treatment per patient amounted to 12,215€ for sorafenib, 13,419€ for TACE and 26,106€ for TARE; variability in treatment patterns among centres was observed. CONCLUSIONS: The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare Service for different treatments used in intermediate and advanced HCC highlighting the need for future research and analysis of the cost- effectiveness of TACE alone or combined with sorafenib, in the treatment of HCC.