Background: Transarterial chemoembolization (TACE) is indicated for unresectable hepatocellular carcinoma. Methods: This was a retrospective study of 50 hepatocellular carcinoma patients treated with TACE using doxorubicin-loaded LifePearl™ to investigate the safety and efficacy of TACE. Results: There was no 30-day mortality, and limited adverse events were reported. At best tumor response, complete response and disease control were 58% and 94%, respectively, with a median of 4.5 months of follow-up. Median overall survival was 33.8 months. Patients with Barcelona Clinic Liver Cancer stage 0 and stage A at best tumor response showed a higher complete response rate (83%) than patients with Barcelona Clinic Liver Cancer stage B (complete response: 50%; p = 0.0414). Conclusion: Doxorubicin-loaded LifePearl™ TACE might be an effective treatment, with a good safety profile, for patients with early/intermediate-stage hepatocellular carcinoma. Further prospective data, especially with a small cohort of selected patients, are required to confirm these results.