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Background: Neoangiogenesis plays a crucial role in the progression of hepatocellular carcinoma (HCC), and concerns have been raised about the role of neoangiogenesis on the effectiveness of transarterial chemoembolization (TACE)., Aim: In this study, we aimed to evaluate Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Inducible Factor-1α (HIF-1α) as circulating prognostic biomarkers in HCC patients treated with TACE., Methods: Blood samples were collected from 163 patients before (t 0 ) and four weeks after TACE (t 1 )., Results: Higher levels of VEGF after TACE were demonstrated (264.0 [78.7-450.8] vs. 278.6 [95.0-576.6] pg/mL; p < 0.0001). Responders to TACE had lower levels of VEGF than non-responders both at t 0 (200.0 [58.9-415.8] vs. 406.6 [181.4-558.6] pg/mL; p = 0.006) and at t 1 (257.3 [68.5-528.6] vs. 425.9 [245.2-808.3] pg/mL; p = 0.003), and in both groups there was an increase in VEGF compared to measurements before treatment (p = 0.001 and p = 0.005, respectively). VEGF was not associated with overall survival (OS), while patients with HIF-1α ≤ 0.49 ng/mL showed better prognosis (median OS 28.0 months [95% CI 19.7-36.3] vs. 17.0 months [95% CI 11.1-22.9]; p = 0.01). Moreover, HIF-1α was identified as an independent prognostic parameter., Conclusions: VEGF and HIF-1α can be considered useful prognostic biomarkers in HCC patients treated with TACE., Competing Interests: Conflict of Interest The Authors declare no potential conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)