Abstract: OBJECTIVE: To investigate the sedative effect and safety of morphine on mechanical ventilation in children with severe hand-foot-mouth disease (HFMD). METHODS: 94 children with severe HFMD who were treated in our hospital from June 2016 to January 2018 were randomly divided into experimental group and control group according to the random number table method, with 47 cases in each group.Children were given mechanical ventilation and conventional drug therapy in both groups.In the control group, children were given intravenous midazolam, and those in the experimental group were given morphine intravenously.Compared the Ramsay scores before sedation, 1h, 4h, 12h and 24h after sedation, various clinical indicators,the level of various indicators and the prognosis of children after mechanical ventilation for 12h between the two groups. RESULTS: The Ramsay scores at each time point after sedation were higher than those before sedation, and the Ramsay scores of the experimental group were higher than those of the control group at 1h and 4h after sedation (P<0.05).The time of onset of the drug, the time of satisfactory sedation, the time of mechanical ventilation and the time of admission to the intensive care unit were shorter in the experimental group than in the control group (both P<0.05).After 12 hours of mechanical ventilation, the oxygenation index (OI) of the experimental group was significantly higher than that of the reference group, and the peak inspiratory pressure (PIP) was lower than that of the reference group (both P<0.05).There was no significant difference in the incidence of adverse reactions and mortality rate between the two groups (all P>0.05).CONCLUSION: Morphine has a significant sedative effect in mechanical ventilation therapy in children with severe HFMD. It can quickly achieve satisfactory sedation, improve the symptoms of hypoxia, reduce mechanical ventilation time and stay in the intensive care unit, and it is safe.