ObjectiveTo analyze the efficacy of ketogenic diet (KD) in the treatment of epilepsy syndrome associated with Electrical status epilepticus during sleep (ESES) and the changes of electroencephalogram (EEG). MethodsThe clinical data of 58 children with ESES-related epilepsy syndrome and cognitive impairment admitted to the outpatient and inpatient department of Xuzhou Children’s Hospital from March 2020 to June 2022 were collected. They were divided into observation group (group A) and control group (group B) by random number table method, with 29 cases in each group. On the basis of not changing the original anti-seizure drugs, group A was treated with ketogenic diet, and group B was treated with hormone. The clinical efficacy, cognitive function and Spike-wave index (SWI) of children with ESES-related epilepsy syndrome were observed before and 3 and 6 months after ketogenic diet and hormone treatment. Results The total clinical effective rate and control rate of group A after 3 months of treatment; The total effective rate and significant efficiency of EEG and the verbal quotient, operation quotient and total intelligence quotient of Wechsler Intelligence Scale for children were significantly lower than those of group B, and the differences were statistically significant (P<0.05). However, the total clinical effective rate and control rate of group A after 6 months of treatment; The total effective rate and significant efficiency of electroencephalogram and the verbal quotient, operation quotient and total intelligence quotient measured by Wechsler Intelligence Scale for children were similar to those of group B, and the difference was not statistically significant (P>0.05). There were no cases of EEG SWI and recurrent clinical symptoms in group A during the follow-up period; In group B, the recurrence rate of EEG SWI was 55.2%, and the recurrence rate of clinical symptoms was 37.9% after 6 months of treatment. There were no serious adverse reactions in the two groups during the treatment period. In group A, about 27.6% (8 cases) of the children had gastrointestinal symptoms, but they were mild and quickly relieved, and no serious adverse reactions occurred in the maintenance period. However, 89.7% (26 cases) of the children in group B showed different degrees of weight gain, and 69% (20 cases) of them showed kexing features such as full moon face and buffalo back. ConclusionsKetogenic diet can improve the curative effect and EEG changes of children with ESES related epilepsy syndrome, and improve their cognition. Compared with hormone pulse therapy, the recurrence rate of ESES related epilepsy syndrome in the treatment of ketogenic diet is lower, and the incidence of adverse reactions is relatively mild and low.