Objective To analyze the characteristics of influenza incidence and the changes of innate immune cells among children who visited the pediatric outpatient or emergency department of a hospital in Shanghai from Jan. 2019 to Dec. 2023, so as to provide references for the prevention of influenza in children. Methods Influenza-like illness (ILI) children who first visited the pediatric outpatient or emergency department of The First Affiliated Hospital of Naval Medical University from Jan. 2019 to Dec. 2023, and underwent influenza virus antigen or nucleic acid testing were enrolled. Their clinical and laboratory data were collected for retrospective analysis. With a month as the basic monitoring unit, a line chart was used to describe the changes in the number of influenza cases and the positive rate. Then, these cases were assigned to pre-coronavirus disease 2019 (COVID-19) group (Jan. 2019 to Dec. 2019), mid-COVID-19 group (Jan. 2020 to Dec. 2022), or post-COVID-19 group (Jan. 2023 to Dec. 2023), and the influenza positive rates among these groups were compared. To further observe the changes of the innate immune cells of children with influenza A after non-pharmacological intervention (NPI) measures, considering the development characteristics of children’s white blood cells, children with influenza A were assigned to 2 subgroups according to age: 0-6 years or 7-16 years. Within each subgroup, they were assigned to pre-NPI group or post-NPI group according to time. A ratio of 1∶1 matching was carried out according to gender and age using propensity score matching, and the blood routine parameters were compared between the 2 groups. Results A total of 41 028 ILI children were enrolled. During the COVID-19 period from Jan. 2020 to Dec. 2022, the influenza positive rates decreased significantly (P＜0.001), and almost no influenza virus was detected. The peak of influenza reappeared in Mar. 2023, with a lag in the peak period, but higher than previous years’ peak, and the speed of reaching the peak was faster. In each subgroup, the white blood cell count and lymphocyte ratio of children with influenza A in the post-NPI group were lower than those in the pre-NPI group (all P＜0.001), and the monocyte ratio was higher than that in the pre-NPI group (both P＜0.001). Conclusion The implementation of NPI measures during COVID-19 leads to disruption of influenza transmission route and changes in the epidemic trend of influenza. The influenza virus causes serious public health problems after COVID-19 period, and children with influenza A experience more serious immune response. It is recommended to strengthen the vaccination of influenza vaccine before the flu season.