Objective To summarize the epidemiological characteristics and drug resistance rate of Mycoplasma pneumoniae (MP) infection in hospitalized children from April to October 2023, and analyze the clinical and therapeutic characteristics of MPP children during this period. Methods Throat swab samples of children with community-acquired pneumonia were collected on the day of hospitalization. The tNGS pathogen and MP macrolide-resistance gene mutation were detected, and MP positive rate and MP macrolide-resistance rate were analyzed. Patients with MPP were grouped by the admission date into non-epidemic group (June) and epidemic group (September), and further divided into resistant group and sensitive group in accordance to whether the macrolide-resistance genes were positive or not. The clinical features of the children were compared among the groups. The treatment differences were discussed comparatively between the non-epidemic resistant group and the epidemic resistant group. Results The median age of 1425 children (686 boys and 739 girls) with community-acquired pneumonia was 6 (3-8) years, and the MP positive rate was 57.1% (813 cases). The positive rate of MP varied significantly from April to October for each month (P<0.001), and MP positive rate increased month by month (12.5%-71.6%). Among 813 hospitalized children with MPP, 627 were positive for macrolide-resistance gene mutation, and the total drug resistance rate of MP was 77.1%. The drug resistance rate of MP was 93.9% in the period of non-epidemic (April to June), and significantly decreased to 71.9% in the epidemic period (August to October). The drug resistance rate of MP varied significantly from April to October for each month (P<0.001). There were 76 children in the non-epidemic group and 189 in the epidemic group. Compared with the non-epidemic group, the length of hospital stay were longer and the levels of CRP and LDH were higher in the epidemic group, with statistical significance (P<0.05). There were 64 children in the sensitive group and 201 in the resistant group. Compared with the sensitive group, the hospital stay was longer and the LDH level was higher in the resistant group, and the difference was statistically significant (P<0.05). Of the 201 children with macrolide-resistant MPP, 71 were in the non-epidemic resistant group and 130 were in the epidemic resistant group. Compared with the non-epidemic resistant group, the time to defervescence after methylprednisolone was longer and the use rate of tetracycline antibiotics was higher in the epidemic resistant group, and the difference was statistically significant (P<0.05). Conclusions The epidemic period of MP is from August to October 2023. Compared with normal days, the infection rate of MP is higher during the epidemic period, but the macrolide-resistant rate of MP in hospitalized children is lower. MPP during this epidemic period triggered stronger immune response, displayed as longer hospital stay and higher inflammatory factor level. The possibility of a new prevalent strain should be considered. This prevalent strain was less sensitive to combine treatment of macrolide plus corticosteroids, and tetracycline drugs are needed to control infection.