Hepatocellular carcinoma (HCC) has the sixthhighest new incidence and third-highest mortality worldwide. Transarterial embolization/chemoembolization (TAE/TACE) remains the gold standard for treating unresectable HCC.However, the therapeutic effect is still unsatisfactory due to the worsening of the postembolization tumor microenvironment (e.g. hypoxia, reduced pH, angiogenesis and immunosuppression), which increases the risks of the tumor recurrence and metastasis. To address these issues, we have conducted translational research from bench to bedside on innovative inorganic interventional biomaterials. This review mainly summarizes our recent work on enhancing TAE/TACE therapy via innovative materials that regulate the tumor microenvironment, reverse immunosuppression and synergize with exogenous stimuli, and introduces the early clinical exploration of the developed microspheres that have brought substantial therapeutic benefits to HCC patients. Finally, this review also highlights the limitations and future directions in TACE to accelerate the clinical translation of these inorganic interventional biomaterials.