This study investigates the efficacy of transarterial chemoembolization (TACE) in treating hepatocellular carcinoma (HCC) and explores the underlying mechanisms of TACE refractoriness. The research identifies that aberrant metabolic reprogramming and immunosuppression contribute to TACE refractoriness, with Rhein, a natural compound, being optimized to sensitize tumors to TACE therapy. Rhein is shown to inhibit glycolysis and induce immunogenic cell death, activate dendritic cells, and enhance MHC class I presentation to CD8+ T cells. The study develops a Pickering emulsion using Rhein nanogel-stabilized lipiodol, which exhibits efficient embolization and sustained drug release. This carrier-free emulsion demonstrates enhanced embolization and tumor suppression compared to conventional methods, and it also activates anti-tumor immune responses. The findings suggest that the Rhein nanogel-stabilized lipiodol emulsion is a promising strategy for improving TACE treatment outcomes in HCC.This study investigates the efficacy of transarterial chemoembolization (TACE) in treating hepatocellular carcinoma (HCC) and explores the underlying mechanisms of TACE refractoriness. The research identifies that aberrant metabolic reprogramming and immunosuppression contribute to TACE refractoriness, with Rhein, a natural compound, being optimized to sensitize tumors to TACE therapy. Rhein is shown to inhibit glycolysis and induce immunogenic cell death, activate dendritic cells, and enhance MHC class I presentation to CD8+ T cells. The study develops a Pickering emulsion using Rhein nanogel-stabilized lipiodol, which exhibits efficient embolization and sustained drug release. This carrier-free emulsion demonstrates enhanced embolization and tumor suppression compared to conventional methods, and it also activates anti-tumor immune responses. The findings suggest that the Rhein nanogel-stabilized lipiodol emulsion is a promising strategy for improving TACE treatment outcomes in HCC.