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Backgrounds & Aims The aim of this study is to evaluate the prognostic significances of not only the initial and the best response during repeated transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), but if eligible, also the time point of achieving treatment responses. Methods Three hundred and fourteen treatment-naïve patients with well-preserved liver function undergoing TACE were recruited. Treatment responses were assessed using modified Response Evaluation Criteria in Solid Tumors. Overall survival (OS) was analyzed using Kaplan–Meier methods, and Cox regression analysis was performed for multivariate analysis. Results After adjusting other variables, objective response (complete response [CR] and partial response [PR]) as the initial response (adjusted hazard ratio [HR] 0.410) and the best response (adjusted HR 0.335) had independent prognostic significances for OS, respectively (both p <0.001). Objective responders as the initial response had the longest OS, followed by patients who subsequently achieved objective response after at least two sessions and those who did not achieve objective response during treatment course eventually (52.6, 27.0, and 10.8 months, respectively; log-rank test, p <0.001). Likewise, patients with CR as the initial response had the longest OS, followed by those who subsequently achieved CR after at least two sessions and those who achieved PR as the best response (70.2, 40.6, and 23.0 months, respectively; log-rank test, p <0.001). Large (>5 cm) and multiple (⩾4) tumors were independently associated with failure to achieve CR after the initial TACE (both p <0.05). Conclusion Both the initial and the best response predicts OS effectively. However, achievement of treatment response at an early time point is still the most robust predictor for favorable outcomes. [ABSTRACT FROM AUTHOR]