Objective To evaluate the safety and effectiveness of intraluminal implantation of 125I seeds strand combined with stent placement in treating malignant biliary obstruction. Methods During the period from June 2009 to June 2013, a total of 68 patients with malignant biliary obstruction were admitted to Shanghai Zhongshan Hospital. Interventional management was carried out in all patients. The clinical data were retrospectively analyzed. Of the 68 patients, intraluminal implantation of 125I seeds strand combined with simultaneous stent placement was performed in 41 (combination therapy group) and only stent placement was employed in 27 (conventional therapy group). The survival time, the improvement of obstructive jaundice, recurrence of jaundice and procedure-related adverse events were recorded, and the results were compared between the two groups. Results Implantation of 125I seeds strand and stent placement were successfully accomplished in all patients. Statistically significant differences in serum bilirubin levels, which were separately determined at 7 days and 14 days after the treatment, existed between the two groups (P<0.05). No obvious marrow depression was observed in the combination therapy group. The median survival time of the conventional therapy group and the combination therapy group was 123 days and 215 days respectively. The difference was statistically significant (P < 0.05). Conclusion For the treatment of malignant biliary obstruction, combination use of intraluminal brachytherapy and stent placement is clinically more safe and effective than conventional pure stent placement therapy.