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BACKGROUND This study aimed to investigate the potential of drug-eluting bead transarterial chemoembolization (DEB-TACE) as downstaging therapy for subsequent radical treatment in patients with hepatocellular carcinoma (HCC). METHODS Totally, 32 patients with unresectable HCC were enrolled, then they received DEB-TACE for down-staging therapy followed by radical treatments (surgery, radiofrequency ablation or microwave ablation). The rate of successful down-staging, treatment response (after DEB-TACE and radical therapy), alpha-fetoprotein (AFP), progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS After down-staging therapy with DEB-TACE, successful down-staging rate was 59.4%. With the followed radical treatment, the complete response was 81.3%. Subsequent analysis indicated that CNLC stage (IIb vs. IIa) was an independent risk factor for successful down-staging. Furthermore, AFP level presented a declined trend throughout the time points (before DEB-TACE, after DEB-TACE, and after radical treatment). Additionally, 1-year, 2-year and 3-year accumulating PFS were 68.8%, 40.6% and 31.3%, respectively; 1-year, 2-year and 3-year accumulating OS were 84.4%, 71.9% and 53.1%, respectively. Kaplan-Meier curves exhibited that successful down-staging was correlated with longer PFS and OS, then further Cox's regression analysis verified that successful down-staging was an independent factor for predicting increased OS but not PFS. Besides, child-Pugh stage (B vs. A), CNLC stage (IIb vs. IIa) and AFP abnormal after radical treatment were independent factors for decreased PFS or OS. CONCLUSIONS DEB-TACE has potential as an additionally effective down-staging therapy for radical treatments, and successful down-staging treatment by DEB-TACE associates with favorable survival profiles in patients with unresectable HCC.