AIM To analyze cytokine levels and to identify their association with outcome in patients with hepatocellular carcinoma(HCC) treated with radiotherapy(RT). METHODS Patients with HCC who were treated with RT were eligible for this prospective study. Blood samples were collected before and after RT, and serum cytokine levels including interleukin(IL)-1, IL-6, IL-8, IL-10, IL-12, and tumor necrosis factor-α were analyzed. RESULTS Between 2008 and 2009, 51 patients were enrolled in this study. Baseline IL-6 level was high in patients with a history of pre-RT treatment. Median survival was 13.9 mo with alpha-fetoprotein(AFP) as a significant factor(P = 0.020). Median failure-free survival(FFS) for infield, outfield-intrahepatic and extrahepatic failures were 23.3, 11.5 and 12.0 mo, respectively. Sex and baseline IL-6 level were associated with infield FFS, and baseline IL-10 level was correlated with outfield-intrahepatic FFS. For extrahepatic FFS, AFP was significant(P =0.034). Patients with a baseline IL-6 level of ≥ 9.7 pg/m L showed worse infield FFS(P = 0.005), and this significance was observed only in treatment-non-na?ve patients(P = 0.022). CONCLUSION In addition to AFP, cytokines seem useful in predicting infield and outfield-intrahepatic failure. Serum cytokines could be useful biomarkers for predicting RT outcome in HCC. AIM To analyze cytokine levels and to identify their association with outcome in patients with hepatocellular carcinoma (HCC) treated with radiotherapy (RT). METHODS Patients with HCC who were treated with RT were eligible for this prospective study. RT, and serum cytokine levels including interleukin (IL) -1, IL-6, IL-8, IL-10, IL- 12, and tumor necrosis factor-α were analyzed. RESULTS Between 2008 and 2009, 51 patients were enrolled in This study. Baseline IL-6 level was high in patients with a history of pre-RT treatment. Median survival was 13.9 mo with alpha-fetoprotein (AFP) as a significant factor ) for infield, outfield-intrahepatic and extrahepatic failures were 23.3, 11.5 and 12.0 mo, respectively. Sex and baseline IL-6 level were associated with infield FFS, and baseline IL-10 level was correlated with outfield-intrahepatic FFS. For extrahepatic FFS , AFP was significant (P = 0.034). Patients w ith a baseline IL-6 level of ≥ 9.7 pg / m L showed worse infield FFS (P = 0.005), and this significance was observed only in treatment-non-naïve patients (P = 0.022). CONCLUSION In addition to AFP , cytokines seem useful in predicting infield and outfield-intrahepatic failure. Serum cytokines could be useful biomarkers for predicting RT outcome in HCC.