Objective To analyze the epidemiological characteristics of nosocomial Escherichia coli infection and risk factors of ESBLs-producing Escherichia coli infection in children, and to provide scientific basis for better prevention of nosocomial Escherichia coli infection in children. Methods A total of 169 children with nosocomial infection hospitalized in Handan Regional Children's Hospital from January 2020 to December 2020 were selected by random sampling method. After specimen collection, bacteria were identified by VitEK-32 identification system , and drug sensitivity of isolated pure Escherichia coli colony was identified by automatic drug sensitivity analyzer Phoenix 100. Statistical analysis of drug resistance of Escherichia coli. The clinical data of the children were retrieved from the case system by uniformly trained professionals, and the department distribution, underlying diseases, clinical characteristics, antibiotic resistance, length of hospital stay, surgery, invasive exercises and other clinical data of all the children were counted. Factor logistic regression analysis of the risk factors of nosocomial infection of ESBLs Escherichia coli in children in the hospital. Results A among of 39 strains of Escherichia coli were detected in children with nosocomial infection in children's hospital. The main specimens were 22 strains (56.41%) in sputum, 11 strains (28.21%) in urine and 6 strains (15.38%) in blood.Twenty-one strains of ESBLs Escherichia coli were detected, with a positive rate of 53.85%. Fever was the most common first symptom in 37 cases (94.87%). Children with ESBLs (+) Escherichia coli infection were significantly higher than those with ESBLs (-) Escherichia coli in age, length of hospitalization, neonates/recent use of broad-spectrum antibiotics, complicated underlying diseases, and invasive operation (P<0.05). Multivariate logistic regression analysis showed that recent use of antibiotics, combined with underlying diseases, and invasive operation were independent risk factors for ESBLs infection in children in hospital (P<0.05). Conclusion The incidence of nosocomial Escherichia coli infection in children is high, and active intervention should be carried out for children who have recently used antibiotics, complicated with underlying diseases, and invasive operations to reduce the risk of ESBLs Escherichia coli infection.