Reserved liver function is one of the most important determinants of survivial in advanced hepatocellular carcinoma (HCC). Especially in cirrhotic patient with decompensated liver function, sorafenib for HCC with main portal vein invasion have limited efficacy and survival benefit. Therefore many clinicians or centers still try locoregional therapy (LRT) such as transarterial chemoembolization (TACE), radiation therapy (RT), or combination with LRT and sorafenib in this situation. However this multidisciplinary approach may increase treatment related toxicity such as liver failure, etc. Recently, studies for combination of RT and sorafenib for HCC with portal vein invasion have been tried and reported not only better therapeutic efficacy, but also more hepatic toxicity.Based on above suggestions, we herein offer our experience of a patient that although achieved survival gain via partial remission of intrahepatic tumor and main portal vein thrombosis and metastatic lymph node by combination therapy of RT and sorafenib, finally expired due to hepatictoxicity. Further study, maybe regarding a combination of locoregional and systemic therapy, is necessary on how to manage decompenstated cirrhotic patients with HCC with main portal vein invasion. (J Liver Cancer 2014;14:120-126)