<b><i>Introduction:</i></b> Sorafenib (SOR) has proved to be effective in patients with advanced hepatocellular carcinoma (HCC), since overall survival was higher in phase III clinical trials; however, disease progression can occur. <b><i>Objectives:</i></b> The study aimed to describe real-life experience in advanced HCC treatment with SOR at a university hospital in Brazil and to estimate the number of patients with indication of second-line therapy. <b><i>Methods:</i></b> This is a retrospective study that included cases of HCC with prescription of SOR based on real-life practice between 2011 and 2016. Demographic, clinical, and laboratory data were collected. <b><i>Results:</i></b> From 572 patients with HCC, SOR was prescribed in 103 cases. From them, 62.1% were classified as Child-Pugh (CP)-A, 54.4% as Barcelona Clinic Liver Cancer (BCLC)-C, and 74 (71.8%) started treatment. Overall survival was 25.5 (95% CI 17.0–34.1) months and 1-year survival was greater in patients who received SOR than in non-treated (88.7 vs. 44.4%, <i>p</i> &#x3c; 0.001). There was no difference in survival between BCLC-B and C (<i>p</i> = 0.405), as well as CP-A and B (<i>p</i> = 0.919). In 21.6% of the patients, a second-line therapy with regorafenib was indicated. <b><i>Conclusion:</i></b> In this real-life study, SOR significantly increased the survival rate by 1 year in patients with advanced HCC regardless of BCLC staging and CP score. Second-line therapy would be indicated in 21.6% of cases.