The efficacy of sorafenib in hepatocellular carcinoma (HCC) has been demonstrated in two pivotal clinical trials: the European SHARP trial and a second trial that recruited patients in the Asia-Pacific region. Sorafenib was approved for the treatment of advanced HCC in Japan based on the results of these studies. This article presents experiences with sorafenib in patients with HCC at three institutions in Japan, representing the viewpoints of a liver surgeon and a hepatologist at university hospitals, and a hepatologist at a community hospital. The three physicians discuss representative cases and current clinical practice at their institutions, and their recommendations for the use of sorafenib in the wider clinical setting. Overall, the experiences at these institutions show that sorafenib is most effective when administered for a long time, and the management of adverse events (AEs) [including dose-reduction and modification] is critical to achieving high levels of adherence to treatment. A team-focussed treatment strategy that includes patient counselling and follow-up can contribute to managing AEs to ensure successful continuation of sorafenib therapy. In addition, a proposed definition of unresponsiveness to transarterial chemoembolization and the implications of treatment lag on the outcomes of sorafenib therapy, as well as measures for the prevention and treatment of hand-foot skin reaction are discussed.