OBJECTIVE: This study aims to explore whether intratumoral and peritumoral ultrasound radiomics of ultrasound images can predict the low expression status of human epidermal growth factor receptor 2 (HER2) in HER2-negative breast cancer patients. METHODS: HER2-negative breast cancer patients were recruited retrospectively and randomly divided into a training cohort (n = 303) and a test cohort (n = 130) at a ratio of 7:3. The region of interest within the breast ultrasound image was designated as the intratumoral region, and expansions of 3 mm, 5 mm, and 8 mm from this region were considered as the peritumoral regions for the extraction of ultrasound radiomic features. Feature extraction and selection were performed, and radiomics scores (Rad-score) were obtained in four ultrasound radiomics scenarios: intratumoral only, intratumoral + peritumoral 3 mm, intratumoral + peritumoral 5 mm, and intratumoral + peritumoral 8 mm. An optimal combined nomogram radiomic model incorporating clinical features was established and validated. Subsequently, the diagnostic performance of the radiomic models was evaluated. RESULTS: The results indicated that the intratumoral + peritumoral (5 mm) ultrasound radiomics exhibited the excellent diagnostic performance in evaluated the HER2 low expression. The nomogram combining intratumoral + peritumoral (5 mm) and clinical features showed superior diagnostic performance, achieving an area under the curve (AUC) of 0.911 and 0.869 in the training and test cohorts, respectively. CONCLUSION: The combination of intratumoral + peritumoral (5 mm) ultrasound radiomics and clinical features possesses the capability to accurately predict the low-expression status of HER2 in HER2-negative breast cancer patients.