To develop an ultrasound (US)-based radiomics score for preoperative prediction of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Between January 1, 2012, and October 31, 2017, a total of 482 HCC patients who underwent contrast-enhanced ultrasound (CEUS) were retrospectively reviewed. The study population was divided into a training cohort (n = 341) and a validation cohort (n = 141) based on a cutoff time of January 1, 2016. Radiomics features were extracted from the grayscale US images of HCC. After features selection, a radiomics score was developed from the training cohort. The incremental value of the radiomics score to the clinic-pathological factors for MVI prediction was assessed in the validation cohort with respect to discrimination, calibration, and clinical usefulness. The US-based radiomics score consisted of six selected features. Multivariate logistic regression analysis showed that the radiomics score, alpha-fetoprotein (AFP), and tumor size were independent predictors of MVI. The radiomics nomogram (based on the three factors) showed better performance for MVI detection (area under the curve [AUC] 0.731[0.647, 0.815] than the clinical nomogram (based on AFP and tumor size) (0.634 [0.543, 0.724]) (p = 0.015). Both nomograms showed good calibration. Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the clinical nomogram. The US-based radiomics score was an independent predictor of MVI in HCC. Combining the radiomics score with clinical factors improved the prediction efficacy. • Radiomics can be applied in US images. • US-based radiomics score was an independent predictor of MVI. • Radiomics nomogram incorporated with the radiomics score showed good performance for MVI prediction.