Background: To analyze the safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) under the combination treatment with immune checkpoint inhibitors (ICI) in unresectable hepatocellular carcinoma (HCC). Methods: In this retrospective single-institution study, 208 HCC patients (152 male and 56 female; mean age, 64.70±11.46 years) who received DEB-TACE between 2018.Nov and 2021.Dec were enrolled. There were 74.0% patients had Barcelona Clinic Liver Cancer stage B HCC, 90.4% were Child-pugh A patients, 63.0% patients had albumin-bilirubin (ALBI) grade 2, and 51.0% patients were up-to-seven out. Among them, 50 patients (24.0%) who received ICI with interval less than 30 days with DEB-TACE were categorized as DEB-ICI group; the remaining 158 patients (76.0%) were categorized as DEB group. ALBI grade before and 90 days after DEB-TACE were recorded to evaluate liver function change. Complications within 90 days after DEB-TACE were considered as TACE-related and were compared between two groups. Results: DEB-ICI group had significant higher incidence rate of liver abscess than DEB group (14.0% versus 5.1%, p=0.0337); other TACE-related complications showed no difference between two groups. There were 23.9% patients in DEB-ICI group had elevated ALBI grade after DEB-TACE, which revealed no difference in comparison with 22.4% in DEB group (p=0.8460). Univariate analysis confirmed that combination with ICI was an independent risk factor of liver abscess formation after DEB-TACE (odds ratio = 3.0523, 95% confidence interval: 1.0474-8.8947, p=0.0409). Among DEB-ICI group, patients received ICI before DEB-TACE had a trend to have higher risk of liver abscess formation than those who received DEB-TACE before ICI (23.8% versus 6.9%, p-value=0.0922). Conclusions: Combination treatment of ICI with DEB-TACE with interval less than 30 days increased risk of liver abscess formation after DEB-TACE.