456 Background: Sorafenib is an orally active multi-kinase inhibitor that has been approved for the treatment of advanced hepatocellular carcinoma (HCC). Advanced HCC patients often exhibit two co-existing and life-threatening factors, cancer and cirrhosis, complicating prognostic evaluations. The present study investigated the survival and causes of death of HCC patients with extrahepatic metastases in the sorafenib era. Methods: We retrospectively analyzed 72 HCC patients with extrahepatic metastases who had received sorafenib. The causes of death among the HCC patients were classified as either hepatic causes (HC) or non-hepatic causes (NHC). Each cause of death was analyzed in the two subgroups. We then compared and assessed their clinical features and outcomes using the Chi square test, the Kaplan-Meier method, and a multivariate analysis. Results: Of the 72 HCC patients (female/male, 12/60), 50 patients had died at the time of the analysis. The median age was 66 (range, 30-84) years. At the time when sorafenib was started, the number of patients with a performance status of 0, 1, or 2 was 63 (88%), 8 (11%), and 1 (1%), respectively, and the number of patients with Child-Pugh class A, and B were 67 (93%), and 5 (7%), respectively. The median survival time and the 1-year survival rate were 11.8 (95% confidence interval 5.3-18.3) months and 49.7%, respectively. The incidence of HC and NHC was 29 (58%) and 21 (42%), respectively. Differences between the HC group and the NHC group were examined according to the patient characteristics, and the following significant differences were observed: main portal vein invasion (P<.05), intrahepatic tumor stage (P<.05), alpha-fetoprotein (AFP) (P<.05), and the des-gamma-carboxy-prothrombin level (P<.05). A multivariate analysis showed that portal vein invasion (hazard ratio [HR] = 2.29, P<.05), a Child-Pugh B status (HR = 7.19, P<.01), and high serum levels of AFP (HR = 2.18, P<.05) were independent predictors of a poor outcome, respectively. Conclusions: This study revealed differences in the clinical characteristics at the time of the start of sorafenib between patients with HC and NHC death. The present results may be useful in the design and analysis of future clinical trials.