Current guidelines recommend transarterial chemoembolization (TACE) as the standard treatment of Barcelona-Clinic Liver Cancer (BCLC)-B patients. However, the long-term survival outcomes of patients managed with this technique do not appear fully satisfactory; in addition, intermediate-stage hepatocellular carcinoma (HCC) includes a heterogeneous population of patients with varying tumour burdens, liver function and disease aetiology. Therefore, not all patients with intermediate-stage HCC may derive similar benefit from TACE, and some patients may benefit from other treatment options, which are currently approved or being explored. These include different TACE modalities, such as selective TACE or drug-eluting beads TACE and radioembolization. The introduction of sorafenib in the therapeutic armamentarium for HCC has provided a new therapeutic option for the treatment of BCLC-B patients who are unsuitable to TACE or in whom TACE resulted in unacceptable toxicity. In addition, clinical trials aimed at investigating the potential role of this molecule in the treatment of patients with intermediate-stage HCC within combination therapeutic regimens are ongoing. This narrative review will present and discuss the most recent evidence on the locoregional or medical treatment with sorafenib in patients with intermediate-stage HCC.