Retroperitoneal leiomyosarcoma is relatively uncommon. Leiomyosarcoma has accounted for about 5%similar to 10% of soft-tissue sarcoma, and 1/2-2/3 of the primary lesions were retroperitoneal, with a cumulative 5-year survival rate of only 35%. Leiomyosarcoma is one kind of soft-tissue sarcoma with the lowest survival rates due to the invasive growth, difficult treatment, and poor prognosis. The present study reported a case of a 78-year-old male diagnosed as left retroperitoneal leiomyosarcoma, who had received three operations. Computed tomography (CT) demonstrated a mass of approximately 12.9 cm x 6.9 cm x 6.6 cm in his retroperitoneal region. The Eastern cooperative oncology group and numerical rating scale scores of pain were 1 and 5, respectively. Multiple treatment strategies were administered, including the application of drainage and I-125 seed implantation. A total of 90 I-125 seeds were implanted into the tumor through repetitious operations, with 30 seeds each time. Treatment planning system was involved to calculate the source distribution. I-125 seeds with the activity of 0.5 mCi were implanted under the guidance of CT, and dosimetric verification was performed after the operation. D90 (90% minimum prescription dose received by target volume) was 40 Gy. Follow-up was performed after 6 months, and complete response was achieved in the local lesions. However, there was no evidence-based treatment currently and the majority of our knowledge was based on results from case reports, thus further studies would be required.