OBJECTIVE： To observe the clinical efficacy and safety of ambroxol hydrochloride in the treatment of neonatal respiratory distress syndrome. METHODS： 108 cases of neonatal respiratory distress syndrome were randomly divided into control group and observation group， 54 cases in each group. Control group were treated with conventional treatment， such as oxygen inhalation， anti-infection and nutritional support， observation group was additionally treated with 30 mg/kg Ambroxol hydrochloride injection， ivgtt， qd， for continuous treatment of 4-6 d. Clinical efficacy， blood gas indexes [oxygen partial pressure （PaO2）， carbon dioxide partial pressure （PaCO2）]， 12， 24 and 48 h after treatment remission time of clinical symptoms， hospitalization time， changes of X-ray film value， tidal volume （VT） and dynamic lung compliance （Cdyn） in 2 groups were compared， and the incidence of adverse reactions was observed. RESULTS： The total effective rate in observation group was 94.44％， which was significantly higher than control group （51.58％）， the difference was statistically significant （P＜0.05）； there was no significant difference in the blood gas indexes in observation group after 12 h （P＞0.05）， PaO2 was significantly higher than control group and PaCO2 was significantly lower than control group 24 and 48 h after treatment， there was significant difference between 2 groups （P＜0.05）. Remission time of cyanosis， dyspnea， lung moist rales and hospitalization time in observation group were shorter than control group， the difference was statistically significant （P＜0.05）. X-ray film value， Cdyn and VT levels in observation group were significantly higher than control group， the difference was statistically significant （P＜0.05）. The incidence of adverse reactions in observation group was 3.70％， which was significantly lower than control group （18.52％）， the difference was statistically significant （P＜0.05）. CONCLUSIONS： Ambroxol hydrochloride shows obvious efficacy in the treatment of neonatal respiratory distress syndrome， it can improve blood gas indexes and accelerate the recovery from disease， with good safety.