Hepatocellular carcinoma (HCC) is a malignancy with high incidence and poor prognosis. Most patients with HCC are diagnosed at an intermediate-advanced stage, losing the opportunity for surgical resection. Although transcatheter arterial chemoembolization (TACE) is recommended for intermediate-advanced stage HCC, supported by evidence from multiple randomized controlled trials, its efficacy is often limited by high-risk factors such as large tumor burden, vascular tumor thrombosis, arteriovenous shunting, or infiltrative growth pattern. In recent years, accumulating evidence has established hepatic arterial infusion chemotherapy (HAIC) as an effective treatment for intermediate-advanced stage HCC, especially in patients with these high-risk features, as it can significantly enhance local tumor control and prolong survival. Recent studies and clinical practice have demonstrated that TACE and HAIC, as two effective intra-arterial therapies, possess distinct mechanisms of action. Their rational combination allows for technical complementarity, yielding a synergistic anti-tumor effect and further improving outcomes in high-risk patients with intermediate-advanced stage HCC. In this context, based on relevant literature and clinical experience, this article discusses the theoretical rationale, technical essentials, appropriate patient selection, and clinical evidence for combining TACE with HAIC in the treatment of HCC, aiming to provide references for its standardized application and wider clinical adoption.
