Background: Inoperable hepatocellular carcinoma (HCC) is treated by conventional transarterial chemoembolization (cTACE) using cone-beam computed tomography (CBCT) or digital subtraction angiography (DSA). We compared patient survival outcomes between CBCT-cTACE with automated tumor-feeder detection (AFD) software and DSA-cTACE alone in inoperable HCC patients.Methods: We reviewed the data of 337 HCC patients treated by CBCT-cTACE or DSA-cTACE between January 2015 and December 2019. Treatment response, progression-free survival (PFS), overall survival (OS), and complications between the CBCT-cTACE and DSA-cTACE groups were compared. Univariate and multivariate logistic regression analyses examined the potential prognostic factors affecting survival after chemoembolization.Results: Tumor response rates in complete response, partial response, and stable disease at 1 month were 67%, 28%, and 4% in the CBCT-cTACE group and 22%, 48%, and 9% in the DSA-cTACE group, respectively. OS rates of patients in the CBCT-cTACE versus DSA-cTACE groups were 87% versus 54%, 44% versus 15%, and 34% versus 7% at 1, 3, and 5 years, respectively. The CBCT-cTACE group had significantly improved PFS (p < 0.001) and OS (p < 0.001). Multivariate analysis showed that CBCT with AFD software was an independent factor associated with longer OS (hazard ratio, 0.38; p < 0.001).Conclusions: Compared with conventional DSA, combining selective cTACE with CBCT and AFD software leads to better tumor response and prolongs OS in patients with inoperable HCC. [ABSTRACT FROM AUTHOR]