PurposeTo investigate the effect of early transarterial chemoembolization (TACE) refractoriness on hepatocellular carcinoma (HCC) patient survival and to explore whether viable lesions > 50% after two consecutive TACE treatments negatively affect the prognosis of HCC patients.Patients and MethodsFrom January 2014 to August 2017, 323 HCC patients who received TACE as the initial treatment were analyzed. TACE refractoriness was diagnosed according to the Japan Society of Hepatology 2021 version. Propensity score matching (PSM) was used to create a 1:1 matched group (nonrefractoriness vs refractoriness). To determine survival outcomes and prognostic factors, the Kaplan-Meier method and Cox proportional hazards model were used.ResultsIn total, 51.1% of patients developed early TACE refractoriness (n = 165). After PSM, 120 patients from each group were matched and analyzed. The median overall survival (OS) time of the early TACE refractoriness group was significantly shorter than that of the nonrefractory group [21 months (95% CI: 15.7–26.3) vs 34 months (95% CI: 27.5–40.5), p = 0.002]. Thirty-eight patients with viable lesions >50% after two consecutive TACE procedures were identified and matched with patients of non-refractoriness. No significant difference in median OS was observed [35 months (95% CI: 21.6–48.5) vs 31 months (95% CI: 25.4–36.6), p = 0.611]. Multivariate analysis revealed that the BCLC stage, tumor size, tumor capsule, tumor distribution, α-fetoprotein level (AFP), and early TACE refractoriness were independent risk factors for prognosis in HCC patients.ConclusionEarly TACE refractoriness may shorten the OS of HCC patients. However, viable lesions >50% after two consecutive TACE treatments did not impair the survival of patients. It may be inappropriate to consider these patients as having developed TACE refractoriness.