The present study aims to evaluate the effectiveness and safety of the anti-reflux microcatheter during DEB-TACE with DC Bead LUMI (radiopaque beads) for the treatment of hepatocellular carcinoma (HCC).We performed an observational longitudinal prospective monocentric study to analyze all patients with HCC who underwent to DEB-TACE with DC Bead LUMI and anti-reflux microcatheter. Technical success, the presence of residual disease, and clinical success were evaluated. The performance of the anti-reflux microcatheter on the basis of the percentage of tumor covered and the non-target embolization (NTE) was also evaluated.Twenty patients underwent DEB-TACE with DC Bead LUMI and an anti-reflux microcatheter. Technical success was achieved in all cases. Residual disease in the target tumor was observed in 11/20 (55%) of cases and no residual disease was found in 9/20 (45%) of cases. The clinical response at 1-month follow-up was of PD 4/20 (20%), SD 7/20 (35%), and CR 9/20 (45%). No major complications were recorded, and 10% of cases had minor complications. The distribution of beads on post-procedural CBCT, classified according to the percentage of target nodule coverage, was ≥50% in 70% (14/20) of cases and between 30-50% in 30% of cases (6/20). NTE was never registered.