Objective To compare the inpatient medical expenses of children with respiratory diseases before and after the implementation of national group purchasing organization(GPO) in Yunfu City, Guangdong Province, and analyze the influencing factors of inpatient medical expenses. Methods The hospitalized children aged 0~14 with respiratory diseases from 2019 to 2020 in Yuncheng district implemented the GPO were selected. The influencing factors of hospitalization expense were analyzed by single factor and multiple regression statistical methods. Results The average hospitalization expense of children with respiratory diseases before the GPO implemented (4 872.38 yuan) was higher than after (4 620.25 yuan, P<0.05); the drug expense accounted for 35.35% and 27.39% of the hospitalization expense of the insured urban and rural children, and integrated payment accounted for 46.85% and 57.59%. Age, hospitalization days, outcome, comorbidities, disease classification, application of GPO drugs and admission classification were the common influencing factors of hospitalization expense of children with respiratory diseases. Hospitalization expense decreased with the increase of age, good outcome and application of GPO drugs, which was a negative correlation. And there was a positive relationship between the rest factors and the total cost of hospitalization. Conclusions To improve the outcome of children, shorten the average length of stay, doing a good job in drug zone and group procurement can reduce the hospitalization cost of children with respiratory diseases.