Summary. Introduction. Sorafenib, an oral multikinaseinhibitor, is the only targeted agent approved for the treatmentof patients with hepatocellular carcinoma (HCC) afterdemonstration to increase overall survival compared to placeboin two randomized phase III study. GIDEON (Global Investigationof therapeutic DEcisions in HCC and Of its treatmentwith sorafeNib) is the largest, global, non-interventional,prospective study of patients with uHCC (n>3200)treated with sorafenib in real-life clinical practice conditions.Here we report the final analysis of safety and efficacy in theItalian cohort of patients. Methods. Patients with unresectableHCC who are candidates for systemic therapy, and forwhom a decision has been made to treat with sorafenib, areeligible for inclusion. Patients demographics disease characteristicsand treatment history were recorded at baseline visit.Sorafenib dose, concomitant medications, performancestatus, liver function, adverse events and efficacy (survivaland response rate) were collected throughout the study.Results. In the Italian cohort of the GIDEON study 278 patientswere included in 36 centers. The global rate of adverseevents was 81%. Drug-related events accounted for 67%,mostly of grade 1 and 2, and only 8% were classified as serious.The most common were diarrhea (24%), fatigue (23%),dermatological (14%), rash/exfoliation (10%), hypertension(9%), hemorrage/bleeding of gastrointestinal tract (6%).Overall survival was 14.4 months and time to progression6.2 months. Objective responses were observed in 14 patients(5%) with 3 complete responses (1%). Stable diseasesof at least 6 weeks were observed in 113 patients (41%) witha 30% of disease control rate. Discussion. The safety profileof sorafenib in terms of rate and type of adverse events issimilar to that emerged in the global international GIDEONstudy as well as in the pivotal registration studies.