INTRODUCTION: Transarterial chemoembolization (TACE) is frequently used to treat patients with hepa‑ tocellular cancer (HCC) who are not eligible for surgery. The efficacy of TACE treatment can be improved by percutaneous insertion of 125I seeds after the procedure. AIM: This meta‑analysis aimed to assess the relative safety and efficacy of TACE with 125I seed insertion (TACE‑I) as compared with TACE alone for the management of inoperable HCC. MATERIALS AND METHODS: The PubMed, Cochrane Library, and Wanfang databases were searched for relevant studies published since the database inception through October 2024. The primary study outcome was objective response rate (ORR), while secondary outcomes comprised disease control rate (DCR), progression‑free survival (PFS), overall survival (OS), and adverse event incidence. RESULTS: This meta‑analysis ultimately included 5 articles, all of which were published in China. In all these studies, TACE‑I outperformed TACE alone with respect to patient ORR (P <0.001), PFS (P <0.001), and OS (P <0.001). DCR values were similar in both groups (P = 0.77), as were the rates of adverse events, including fever (P = 0.75), vomiting (P = 0.83), and myelosuppression (P = 0.23). The only outcome exhibiting significant heterogeneity was OS (I2 = 73%). Based on the Egger test, the end points affected by publication bias were ORR, DCR, and OS (P = 0.01, P = 0.03, and P = 0.04, respectively). CONCLUSIONS: In patients with inoperable HCC, TACE‑I is associated with significantly better efficacy and longer survival than TACE alone, and has a good safety profile.