〔Abstract〕 Objective To explore the clinical effect of ambroxol hydrochloride combined with nasal positive airway pressure ventilation in the treatment of newborns with respiratory failure. Methods 60 newborns with respiratory failure treated in Huidong County People's Hospital from January 2017 to January 2020 were randomly divided into control group and observation group with 30 cases in each group. The control group was treated with ambroxol hydrochloride. On this basis, the observation group was treated with nasal positive airway pressure ventilation, and the trentment effects of the two groups were compared. Results The total effective rate of the observation group was 96.67%, higher than 70.00% of the control group, the difference was statistically significant (P < 0.05); There was no significant difference in arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2) and pH between the two groups before treatment (P > 0.05). After treatment, PaO2 in the observation group was higher than that in the control group, PaCO2 and pH were lower than those in the control group, the differences were statistically significant (P < 0.05); The incidence of adverse reactions in the observation group was 6.67%, lower than 30.00% in the control group (P < 0.05). Conclusion For newborns with respiratory failure, ambroxol hydrochloride combined with nasal positive airway pressure ventilation can correct hypoxemia, reduce mechanical ventilation, reduce costs, improve prognosis and have fewer adverse reactions.