Abstract: Objective To evaluate the curative effect of radiofrequency ablation (RFA) combined with 125I seed implantation in treatment of advanced intrahepatic cholangiocarcinoma (ICC). Methods The clinical data of 48 patients with advanced ICC confirmed by histopathological examination, in our hospital between June 2012 and June 2014 were retrospectively analyzed. A Total of 48 patients were assigned into control group and study group with 24 cases in each group. The study group received the radiofrequency ablation combined with ¹²⁵I seed implantation, while the control group was administrated with systemic venous chemotherapy. The level of tumor markers, short-term results and long-term survival rates of the two groups were compared and analyzed. Results The levels of tumor biomarkers were significantly decreased in both groups after the treatment as compared with their pretreatment levels, but their decreasing amplitudes were significantly greater in the study group than those in the control group (all P<0.05). There was no statistical difference in benefit rate between the study group and control group (75.00% vs. 87.50%, P=0.267), but the response rate in the study group was significantly higher than that in the control group (70.83% vs. 37.50%, P<0.05). The 1-year, 2-year and 3-year survival rates showed no statistical difference between the two groups (all P>0.05), but the over 3-year survival rate in the study group was significantly higher than that in the control group (P<0.05). Conclusion RFA combined with ¹²⁵I seed implantation for advanced intrahepatic cholangiocarcinoma can achieve good short-term effects, increase long-term survival and reduce the level of tumor markers.