Objective To study and analyze the etiological characteristics and drug treatment strategies of co-infection in children with pertussis. Methods A total of 174 hospitalized children diagnosed with pertussis in Zaozhuang Maternal and Child Health Hospital from November 2023 to October 2024 were retrospectively analyzed, and the etiological characteristics and drug treatment strategies of pertussis mixed infection were analyzed. Results Statistics of the distribution of mixed infection pathogens, of 174 children with pertussis with mixed infection, 60 (34.48%), M. pneumoniae infection in 24 (13.79%) and 11 (6.32%), Mixed bacterial infection in 79 cases (45.40%), Compared to the visible, With a high proportion of bacterial infection (P<0.05). Disease treatment-related indicators of children with mixed infection disease of pertussis were higher than those of children with other types of co-infections, and the difference was statistically significant (P<0.05). The number of days of hospitalization in the infant group was higher than in other age groups (P<0.05). Conclusions Pertussis co-infection has a high proportion of children, among which Mycoplasma pneumoniae infection and bacterial infection are common co-infection types, and the disease treatment is implemented for children, and children with pertussis and co-infected pathogens tend to have a longer hospital stay and higher treatment costs.