Purpose: To assess the safety and efficacy of transarterial chemoembolization using a 75-μm drug-eluting embolic (DEE) in patients with unresectable hepatocellular carcinoma (HCC). Materials and Methods: The medical records of 109 patients with a mean age of 64.1 years (range 85–49) treated for unresectable HCC between November 2013 and August 2016 with transarterial chemoembolization using a 75-μm DEE were retrospectively reviewed. Patients who had prior therapy for HCC were excluded. Child-Pugh A patients and Barcelona Clinic Liver Cancer stages A/B patients constituted 68.8% and 65.1% of the patients, respectively. The mean size of the index tumors was 5.8 cm (range 18.5–1.2) with 42 (39%) patients with central tumors around the porta-hepatis region. Portal vein invasion was seen in 10 (9.2%) patients. Tumor response was categorized according to the modified Response Evaluation Criteria in Solid Tumors 1.1, and the toxicity profile was assessed using Common Terminology Criteria for Adverse Events, version 4.03. Results: At 1-month follow-up, complete response, objective response, and disease control was seen in 23%, 66%, and 90%, respectively. The median progression-free survival was 11.2 months. The median overall survival was 25.1 months (33.4 months for Child-Pugh A and 28.2 months for Barcelona Clinic Liver Cancer stages A/B), and transplant-free survival was 21.3 months. The 6-, 12-, and 24-month survivals were 91.7%, 75.5%, and 50.5%, respectively. Grade 3 toxicity was seen in 1.8% of the patients; no grade 4 or 5 toxicity was reported. Conclusions: Transarterial chemoembolization using 75-μm DEE is safe and efficacious in the treatment of HCC.