Background and objective: Sorafenib is the standard treatment for advanced hepatocellular carcinoma. However, no consensus has been reached regarding the criteria for its discontinuation. To study the optimal timing for discontinuation, we performed a prospective evaluation of the effect of continuing Sorafenib for the treatment of progressive disease (PD). Methods: Patients with advanced hepatocellular carcinoma were actively enrolled and administered Sorafenib therapy; for patients requiring further treatment for PD identified in imaging studies, Sorafenib treatment was also continued with the PD used as a new baseline. Treatment was administered until PD was reached a second time, at which point the safety and efficacy of the treatment was evaluated. Results: Thirty patients were enrolled and received Sorafenib treatment, and 20 underwent additional therapy. Of these 20 patients, all were determined to have PD based on a second imaging evaluation. During the continued treatment, no persistent, difficult-to-treat cases were attributed to adverse drug reactions. Of the patients receiving additional therapy, a stable disease (SD) evaluation was obtained in 45% of cases. The criteria for achieving SD with continuous therapy included patients with no PD at the initial treatment evaluation, and those for whom the dosage was increased during treatment. Conclusion: We performed a prospective evaluation of the safety of continuing Sorafenib therapy after PD, and we determined that Sorafenib was well tolerated; this is a treatment option that should be considered when no other second-line therapy is available.