This study investigates the effectiveness and safety of sorafenib in a heterogeneous cohort of Child-Pugh A, B and C patients with advanced hepatocellular carcinoma in a clinical-practice scenario. Adult patients with hepatocellular carcinoma and treated with sorafenib 800 mg/day were eligible for this multicentric retrospective observational study. Safety analyses were performed and the effectiveness of sorafenib was assessed in terms of time to progression (TTP) and overall survival (OS). In total, 93 patients were enrolled: 14 were Child-Pugh A, 70 were Child-Pugh B and nine were Child-Pugh C. No differences in the frequency of grade 3 adverse events among different Child-Pugh classes were reported. In the overall cohort, median OS was 12 months (95% CI: 11.7-12.8 months) and TTP was 3 months (95% CI: 2.5-3.4 months). The Child-Pugh score had a statistically significant effect on TTP: 6.6 months in Child-Pugh A, 2.8 months in Child-Pugh B and 2.0 months in Child-Pugh C patients (p = 0.012). To our knowledge, this study includes the largest cohort of Caucasian Child-Pugh B and C patients ever treated with sorafenib. Although the retrospective design of this study does not allow reaching any definite conclusion, the results could lend some preliminary support to the safety and the effectiveness of sorafenib monotherapy in patients with Child-Pugh B and Child-Pugh C liver function.