ObjectiveTo investigate the value of interictal scalp high-frequency oscillations (HFOs) in localizing the epileptogenic zone (EZ) in children with infantile epileptic spasms syndrome (IESS). Methods A retrospective analysis was conducted on surgical IESS patients treated at the Epilepsy Center of Shenzhen Children’s Hospital from August 2018 to November 2021. Preoperative EEG and clinical data were collected. Based on Engel classification at 2-year follow-up, patients were divided into a seizure-free group (Engel Ia) and a non–seizure-free group (non–Engel Ia). An automated detection system was used to identify ripple events (80–250 Hz), and the H-index (ripples per channel per minute) was calculated in the resection zone (RZ) and non-resection zone (non-RZ). Result 35 children were included (19 seizure-free, 16 non–seizure-free). The H-index in the RZ was significantly higher than in the non-RZ in the seizure-free group [(58.16±43.95) vs. (24.07±22.85), P<0.05]. Using the RZ of the seizure-free group as the gold standard, the area under the ROC curve (AUC) of the H-index for predicting the EZ was 0.83 [95%CI (0.70, 0.96) , P<0.001], with an optimal diagnostic threshold of 21.50 (sensitivity 73.68%, specificity 84.21%). Conclusion The results confirm that the interictal scalp HFO index may serve as a potential biomarker for localizing the EZ in IESS children with structural etiologies.