BACKGROUND: The present study aimed to evaluate the short-term efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres Beads loaded with doxorubicin (DOX) in the treatment of Chinese patients with hepatocellular carcinoma (HCC) compared to conventional TACE (cTACE). METHODS: A total of 54 patients with HCC treated by TACE from June 2016 to February 2017 were retrospectively analyzed. These included 24 cases in the DEB-TACE group and 30 cases in the cTACE group. The clinical efficacy, tumor recurrence rate, and complications were compared between the two groups. Furthermore, liver function tests and alpha-feto protein levels were compared between the two groups before and at 1 week and 1 month after interventional treatment. RESULTS: There were no significant differences in baseline characteristics (p > 0.05). Tumor response rates and disease control rates in the DEB-TACE group were significantly higher than those in the cTACE group at 3 and 6 months after treatment (p < 0.05). Recurrence rates at 6 months were significantly higher for cTACE compared to DEB-TACE (43.3 vs. 16.7%; p = 0.036). At 1 month, the AFP level in the DEB-TACE group was significantly lower than that in the cTACE group (p = 0.008). At the end of follow-up, four cases in the DEB-TACE group and two cases in the cTACE group were treated with salvage surgery after downstaging the disease. Liver function of both groups improved at 1 month. However, alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels in the DEB-TACE group were better than those in the cTACE group (p < 0.05). The incidence of DOX-related complications in the DEB-TACE group was significantly lower than in the cTACE group (p < 0.05). CONCLUSION: The short-term efficacy of DEB-TACE is better, and the complication rates are lower compared to cTACE in the treatment of Chinese patients with HCC. However, long-term clinical efficacy and survival benefit should be analyzed in future studies.