Abstract: Objective　To investigate the efficacy, safety and prognostic factors of intensity modulated radiation therapy (IMRT) combined with sorafenib in the treatment of hepatocellular carcinoma (HCC) with portal vein thrombosis (PVTT). Methods Seventy-six patients of HCC with PVTT were divided into two groups according to whether sorafenib was synchronized or not: IMRT+sorafenib group (n=30) and IMRT alone group (n=46). Clinical data, survival results and adverse reactions were compared between the two groups. Kaplan-Meier method was used to calculate the 2-year overall survival rate (OSR), progression free survival rate (PFSR), distant metastasis free survival rate (DMFSR), and Log-rank test was also used for the detection. The Cox model multivariate analysis was used for prognostic factors. Results The objective response rates (ORR) were 53.3% and 43.5% in IMRT+sorafenib group and IMRT alone group, respectively (P＞0.05). The median survival time was longer in IMRT+sorafenib group than that in the IMRT alone group (12.0 vs. 9.0 months). The 2-year OSR were 23.8% and 3.5% in IMRT+sorafenib group and IMRT alone group (Log-rank χ2=6.271, P=0.012), PFSR were 7.5% and 0 (Log-rank χ2=6.205, P=0.013), and DMFSR were 9.5% and 0 (Log-rank χ2=4.346, P=0.037), respectively. Multivariate analysis showed that AST/ALT＞1.26, tumor unresponsiveness and IMRT alone were independent risk factors for OS (all P＜0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P＞0.05). Conclusion Compared with IMRT alone, IMRT concurrent with sorafenib can improve the long-term efficacy of HCC patients with PVTT, without increasing adverse reactions. The patients with AST/ALT＜1.26, tumor response and concurrent with sorafenib have better prognosis.