OBJECTIVE: This study aims to evaluate and compare the predictive accuracy of Sonazoid-contrast-enhanced ultrasound (CEUS) and Gd-EOB-DTPA-enhanced MRI for detecting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: In this single-center prospective study, we included 64 patients with histopathologically confirmed single HCC lesions. Based on post-operative pathologic data, patients were categorized into two groups: those with MVI (n = 21) and those without MVI (n = 43). The diagnostic efficacy of CEUS was compared with that of MRI in predicting MVI. RESULTS: Multifactorial analysis revealed that US features (tumor size > 4.35 cm, peritumoral enhancement, post-vascular ring enhancement, peak energy in the arterial phase of the difference between the margin area of HCC and distal liver parenchyma <-1.0 × 10 a.u), MRI features (rim enhancement, irregular tumor margin, and the halo sign) were all independent predictors of MVI (p < 0.05). The sensitivity and specificity of CEUS features in predicting MVI ranged from 61.9% to 86.4% and from 42.9% to 71.4%, respectively. For MRI features, the sensitivity and specificity ranged from 33.3% to 76.3% and from 54.7% to 90.5%, respectively. No statistically significant differences were observed in the area under the curve between CEUS and MRI (p > 0.05). Notably, peak energy of the difference showed the highest sensitivity at 86.4%, while the halo sign in MRI exhibited the highest specificity at 90.5%. CONCLUSION: Sonazoid-CEUS and Gd-EOB-DTPA-enhanced MRI demonstrate potential in predicting MVI in HCC lesions. Notably, CEUS showed higher sensitivity, whereas MRI displayed greater specificity in predicting MVI.