Objective: To evaluate the clinical efficacy of 125I radioactive seed implantation in treatment of primary liver cancer. Methods: The clinical data of 84 liver cancer patients undergoing 125I radioactive seed implantation from June 2009 to August 2012 were retrospectively analyzed. Results: A total of 3 630 seeds were implanted in the 84 patients, with an average of 17 seeds for tumor size equal to or less than 35 cm and an average of 46 seeds for tumor size larger than 35 cm, and all patients were successfully implanted in one session. After implantation, the pain of the patients was relieved or disappeared, complete response (CR) was achieved in 40 cases, partial response (PR) was obtained in 36 cases, stable disease (SD) was seen in 8 cases, and the overall effective rate (CR+PR) was 90.5%. Postoperative follow-up ranged from 3 to 45 months, the average survival time of the patients was 16.5 months, and their 1- and 2-year survival rate was 64.3% and 31.0%, respectively. Conclusion: Intratumoral 125I radioactive seed implantation has demonstrable efficacy, and can be used as an alternative treatment modality for refractory, recurrent or metastatic liver cancer.