Microvascular invasion (MVI) is an independent risk factor for the early recurrence and poor survival of HCC. This study aims to investigate the potential clinical value of dynamic contrast-enhanced ultrasound (DCE-US)-Sonazoid in preoperatively assessing MVI in HCC.This single centre prospective study included 140 patients with histopathologically-confirmed single HCC lesions. Patients were classified according to the post-operative pathological information presence of MVI: MVI + group (n = 32) and MVI- group (n = 108). All patients underwent DCE-US within 1 week before surgery. The quantitative perfusion parameters of HCC lesions, margins of HCC lesions, and distal liver parenchyma were obtained and analyzed.Clinicopathological (serum alpha-fetoprotein, Des-gamma-carboxyprothrombin, and pathological grade) and gray-scale imaging features (tumor size) were significantly different between the MVI + and MVI- groups (p < 0.05). Further quantitative analysis showed that when comparing the MVI + and MVI- groups, half-decrease time (HDT) and wash-out rate (WoR) of HCC lesions and peak enhancement (PE) in the arterial phase of difference between the margin area of HCC and distal liver parenchyma were significantly different (p = 0.045, p = 0.035, and p = 0.023, respectively). Combining the above three quantitative parameters, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 69.3% (97/140), 37.8% (17/45), 84.3% (80/95), 53.1% (17/32), 74.1% (80/108), respectively.DCE-US with quantitative perfusion analysis has the potential to predict MVI in HCC lesions.DCE-US with quantitative perfusion analysis has the potential to predict MVI in HCC lesions.