Background. Portal vein tumor thrombosis (PVTT) is a common event in advanced hepatocellular carcinoma (HCC). The optimal treatment for these patients remains controversial. Methods. A retrospective review of 149 patients who had unresectable HCC associated with PVTT between January 2005 and December 2012 was performed. Outcomes related to external beam radiation-based treatment were measured, and clinicopathological features and parameters affecting prognosis were analyzed as well. Results. The radiotherapeutic response of PVTT was an important element that affected the overall treatment response of HCC. Serum α-fetoprotein < 400 ng/mL, the presence of a radiotherapeutic response on PVTT, and receiving additional locoregional therapy were significant prognostic factors affecting the survival of patients. Patients who had received additional locoregional therapy obtained a better outcome, and six of them were eventually able to undergo surgical management with curative intent. Conclusion. The outcome of HCC associated with PVTT remains pessimistic. In addition to the current recommended treatment using sorafenib, a combination of external beam radiotherapy targeting PVTT and locoregional therapy for intrahepatic HCC might be a promising strategy for patients who had unresectable HCC with PVTT. This approach could perhaps offer patients a favorable outcome as well as a possible cure with following surgical management.