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Abstract Background Arterial enhancement fraction (AEF), derived from triphasic CT scans, is considered to indirectly reflect the ratio of hepatic arterial perfusion to total perfusion. The purpose of this study was to retrospectively investigate the relationship between AEF and treatment response and survival in hepatocellular carcinoma (HCC) patients treated with drug-eluting bead (DEB) TACE. Methods AEF of primary lesion (AEFpre) and residual tumor (AEFpost) in 158 HCC patients were obtained from triphasic liver CT examinations pre- and post-treatment. Wilcoxon-signed rank test was used to compare the AEFpre and AEFpost for different response groups. Survival curves for overall survival (OS) in patients with different AEF were created by using Kaplan-Meier method. Cox regression analyses were used to determine the association between AEF and OS. Results There was no correlation between AEFpre and treatment response. After DEB-TACE, AEFpost was significantly lower than AEFpre either in the partial response group (38.9% vs. 52.7%, p <  0.001) or in the stable disease group (49.3% vs. 52.1%, p = 0.029). In the progression disease group, AEFpost was numerically higher than AEFpre (55.5% vs. 53.0%, p = 0.604). Cox regression analyses showed that risk of death increased in patients with AEFpre > 57.95% (HR = 1.66, p = 0.019) or AEFpost > 54.85% (HR = 2.47, p <  0.001), and the risk reduced in patients with any reduction in tumor AEF (decrease ratio ≥ 0) and with increased AEF but not exceeding the ratio of 0.102 (increase ratio <  0.102) (HR = 0.32, p <  0.001). Conclusions The change in AEF of viable tumor is correlated with response of HCC to DEB-TACE. In addition, the AEF could be a helpful predictor in future studies on the embolization treatment for HCC.