Abstract: Objective To explore the clinical efficacy of CT-guided radioactive ¹²⁵I seed implantation in treating retroperitoneal lymph node metastases. Methods From April 2015 to January 2019, 35 patients pathologically confirmed malignant tumor with retroperitoneal lymph node metastasis received CT-guided radioactive ¹²⁵I seed implantation. Three-dimensional images of lymph nodes were reconstructed using the treatment planning system (TPS) before treatment, and the corresponding number and distribution of ¹²⁵I seeds were calculated. CT-guided percutaneous and transhepatic seed implantation. The 1-year survival rate, clinical benefit rate, response rate, and the complications were evaluated. Results Patients were followed up for 5-18 months, with an average of 7 months. Symptoms of refractory pain were significantly resolved, while the Karnofsky score was significantly increased. The 1-year survival rate of 1, 3, 6, 9 and 12 months after operation was 100.00%, 100.00%, 71.42%, 54.29% and 48.57%, respectively. The response rate was 69.49%, 79.66%, 79.49%, 82.39% and 70.97%, respectively. The clinical benefit rate was 89.83%, 91.53%, 84.62%, 85.29% and 77.42%, respectively. Eighteen patients died. There were no serious complications such as particle displacement, postoperative bone marrow suppression, massive hemorrhage, infection, radioactive peritonitis, radioactive enteritis and fistula. Conclusion CT-guided ¹²⁵I seed implantation for malignant tumor with retroperitoneal lymph node metastasis is feasible, safe and effective in improving patient quality of life.