PURPOSE This study aimed to evaluate the efficacy and safety of transarterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) and iodine-125 (125I) seed implantation (TACE-RFA-125I) for recurrent hepatocellular carcinoma (HCC) after hepatectomy. METHODS The study retrospectively analyzed patients with recurrent HCC who received TACE-RFA-125I or TACE-RFA treatment in our institution between January 2013 and January 2023. Overall survival (OS), progression-free survival (PFS), and recurrence were compared between the two groups. RESULTS A total of 187 patients were enrolled in this study, with 105 in the TACE-RFA-125I group and 82 in the TACE-RFA group. There were 67 men and 15 women in the TACE-RFA group, with an average age of 55.4 ± 10.9 years, and 93 men and 12 women in the TACE-RFA-125I group, with an average age of 55.5 ± 10.7 years. The TACE-RFA-125I group exhibited a significantly improved survival benefit compared with the TACE-RFA group (median OS: 49 months vs. 32 months, P < 0.001; median PFS: 24 months vs. 16 months, P < 0.001). The univariate and multivariate analyses revealed that TACE-RFA-125I was a protective factor for OS and PFS. A total of 32 patients in the TACE-RFA group experienced recurrence during follow-up, with local recurrence in 12 cases, intrahepatic recurrence in 10 cases, and extrahepatic metastases in 10 cases. A total of 28 patients in the TACE-RFA-125I group experienced recurrence, 6 with local recurrence, 12 with intrahepatic recurrence, and 10 with extrahepatic metastases. No procedure-related deaths occurred in this study. CONCLUSION In patients with recurrent HCC, TACE-RFA-125I demonstrates promising tumor control and acceptable safety. CLINICAL SIGNIFICANCE This study provides promising clinical guidance for patients with recurrent HCC after hepatectomy and is expected to provide beneficial strategies for the treatment of this disease.