Objectives <p>To explore the dynamic perfusion process features reflected by preoperative high frame rate contrast-enhanced ultrasound (H-CEUS) in predicting the biological characteristics and recurrence of hepatocellular carcinoma (HCC).</p> Methods <p>From April 2021 to April 2024, 105 HCC patients confirmed by pathology received H-CEUS before radical resection. H-CEUS image features related to differentiation grades, microvascular invasion (MVI), Ki-67 levels and glypican-3 (GPC-3) expression were analyzed. Differences in recurrence-free survival (RFS) according to H-CEUS image features were further compared. The diagnostic performance in predicting HCC recurrence was evaluated.</p> Results <p>Arborescent vascular morphology on H-CEUS images was an independent risk factor of MVI, high Ki-67 levels and positive GPC-3 expression (<i>P</i> &lt; 0.05). Conversely, fine vascular morphology was associated with the absence of MVI, low Ki-67 levels and negative GPC-3 expression. HCC with poor differentiation and MVI were more frequently classified as LR-M category. Feeding artery showed a significant difference in GPC-3-positive and GPC-3-negative expression (<i>P</i> &lt; 0.05). Over a median follow-up of 17 months, arborescent vascular morphology was significantly correlated to shorter RFS (<i>P</i> &lt; 0.05) and different from fine vascular morphology in RFS after resection. Both LR-M category and feeding artery were not related to RFS. H-CEUS combined with AFP had a good diagnostic performance in predicting HCC recurrence (AUC = 0.813).</p> Conclusions <p>Vascular morphology reflected by H-CEUS was associated with the biological characteristics of HCC. H-CEUS combined with AFP provides a novel preoperative tool to predict HCC recurrence, which is beneficial to guiding the clinical management of patients.</p>