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Purpose: To compare tumor perfusion on cone-beam computed tomography (CBCT) after hepatic artery infusion port implantation with the tumor response to hepatic arterial infusion chemotherapy (HAIC) in patients with hepatocellular carcinoma (HCC)., Methods: This retrospective study was conducted in patients with advanced HCC treated with HAIC from 2015 to 2020. We performed CBCT with contrast injection via a port on the day following implantation. We classified tumor perfusion on CBCT into three groups: hyperperfusion, isoperfusion, and hypoperfusion. We also evaluated tumor response to HAIC on follow-up images using RECIST 1.1 and compared it with tumor perfusion on CBCT., Results: This study included 206 tumors in 193 patients (mean: 60.5 years) with HCC. There were 100 hyperperfusion tumors (48.5%), 92 isoperfusion tumors (44.7%), and 14 hypoperfusion tumors (6.8%). The tumor response to HAIC included 10 tumors with a complete response (CR) (4.9%), 66 tumors with a partial response (32%), 60 tumors with stable disease (29.1%), and 70 tumors with progressive disease (34%). Hyperperfusion tumors had a 65% objective response rate (ORR) and a 92% disease control rate (DCR). Isoperfusion tumors had a 12% ORR and a 46.8% DCR, while hypoperfusion tumors had a 0% ORR and a 7.1% DCR. A CR was shown only in hyperperfusion tumors. The ORR and DCR of the three groups were different, with statistical significance ( P < 0.001)., Conclusion: Hyperperfusion tumors on CBCT showed a better tumor response to HAIC, with a 65% ORR in patients with HCC. Tumor perfusion on CBCT after implantation of the hepatic arterial infusion port was associated with the tumor response to HAIC.