Jianbing Wu,* An Li,* Jiajin Yang,* Yanjun Lu, Jie Li Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China *These authors contributed equally to this work Background: Transarterial chemoembolization (TACE) and sorafenib (SOR) are well-established treatments for hepatocellular carcinoma (HCC). This study evaluates the efficacy and safety of SOR combined with TACE in the treatment of patients with TACE-refractory, advanced-stage HCC. Methods: This retrospective study included 61 patients with TACE-refractory advanced HCC. Patients were divided into TACE + SOR (n=30) and TACE (n=31) treatment groups. Patient demographic and clinical characteristics, overall survival (OS), time to progression (TTP), disease control rate (DCR), and adverse events (AEs) were compared between the two groups. Results: Compared with TACE alone, the 5-year OS and TTP were prolonged in the TACE + SOR group (median OS: 17.9 vs 7.1 months, P<0.001; median TTP: 9.3 vs 3.4 months, P<0.001). Multivariate analysis showed that Child–Pugh class A (hazard ratio [HR], 0.234; 95% confidence interval [CI], 0.092–0.595), Eastern Cooperative Oncology Group performance status 1 (HR, 0.355; 95% CI, 0.153–0.826), alpha-fetoprotein <400 ng/mL (HR, 0.349; 95% CI, 0.177–0.689), and TACE + SOR treatment (HR, 0.151; 95% CI, 0.071–0.322) were independent, positive predictive factors of OS. Conclusion: The OS and TTP in the combined treatment group were significantly improved when compared with the TACE group. However, no significant difference in DCR was found between these two groups. While no AEs occurred in the TACE group, two patients in the TACE + SOR group experienced severe AEs which were effectively mitigated by lowering the dose of SOR. Thus, SOR in combination with TACE is a safe and effective treatment for advanced-stage, prior-TACE-resistant HCC. Keywords: hepatocellular carcinoma, sorafenib, transarterial chemoembolization, overall survival, time to progression, TACE-refractory, adverse events