Hypoxia is a hallmark of solid tumors, including hepatocellular carcinoma (HCC). Hypoxia has proven to be involved in multiple tumor biological processes and associated with malignant progression and resistance to therapy. Transarterial chemoembolization (TACE) is a well-established locoregional therapy for patients with unresectable HCC. However, TACE-induced hypoxia regulates tumor angiogenesis, energy metabolism, epithelial-mesenchymal transition (EMT), and immune processes through hypoxia-inducible factor 1 (HIF-1), which may have adverse effects on the therapeutic efficacy of TACE. Hypoxia has emerged as a promising target for combination with TACE in the treatment of HCC. This review summarizes the impact of hypoxia on HCC tumor biology and the adverse effects of TACE-induced hypoxia on its therapeutic efficacy, highlighting the therapeutic potential of hypoxia-targeted therapy in combination with TACE for HCC.

Intermediate and advanced-stage hepatocellular carcinoma (HCC) continues to present significant therapeutic challenges. Hepatic artery infusion chemotherapy (HAIC), a well-established locoregional treatment for unresectable HCC, has recently demonstrated promising clinical outcomes both as monotherapy and in combination with systemic therapies. This comprehensive review examines recent clinical advances in HAIC for HCC, with particular emphasis on evolving treatment regimens and their therapeutic efficacy.