Purpose: Transarterial chemoembolization (TACE) delivers cytotoxic drugs intra-arterially and induces ischemic necrosis by arterial embolization. Embolization is achieved using a variety of agents that differ widely in particle size and range, deformation, and in vivo arterial distribution. The clinical significance of these differences has not been thoroughly characterized. The present study is to compare the efficacy of Embosphere and Embozene microspheres in TACE therapy for hepatocellular carcinoma. Materials and Methods: This retrospective study includes 108 hepatocellular carcinoma (HCC) patients who received TACE/doxorubicin with Embozene (70 patients) or Embosphere (38 patients) at a single medical center. Patient outcomes, including liver function, tumor size, tumor response, and complications after treatment, were analyzed. The change in total target lesion size and tumor response was evaluated according to embolization agent and clinical characteristics. Results: The postoperative glutamate oxaloacetate transaminase (mean, 194.5 vs. 147.5; p=0.032) and bilirubin (mean, 1.11 mg/dL vs. 0.73 mg/dL; p=0.016) were higher among patients treated with Embozene, the decrease in the number (55.86±25.55% vs. 41.81±38.51%, p=0.027) and size (56.37±25.91 mm vs. 43.44±37.89 mm, p=0.001) of liver tumors relative to baseline was greater in these patients than in those treated with Embosphere. These greater antitumor effects were achieved using lower doses of doxorubicin than for treatment with Embozene. Minor complications were more common among patients treated with Embosphere than with Embozene. Conclusion These results suggest that Embozene is more efficacious than Embosphere for HCC treatment using TACE/doxorubicin.