Abstract: Objective To investigate the sedative effect and safety of morphine on mechanical ventilation in children with severe hand-foot-mouth disease（HFMD）.Methods A total of 94 children with severe HFMD were randomly divided into experimental group and control group according to the random number table method,with 47 cases in each group.Both groups were given mechanical ventilation and conventional drug therapy.In the control group,children were given intravenous midazolam,and those in the experimental group were given morphine intravenously.The Ramsay scores before sedation,1 h,4 h,12 h and 24 h after sedation,various clinical indicators,the level of various indicators and the prognosis of children after mechanical ventilation for 12 h were compared between the two groups. Results The Ramsay scores at each time point after sedation were higher than those before sedation（P＜0.05）,and the Ramsay scores of the experimental group were higher than those of the control group at 1 h and 4 h after sedation（P＜0.05）.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（P＜0.05）.After 12 hours of mechanical ventilation,the oxygenation index（OI）of the experimental group was significantly higher than that of the control group（P＜0.05）,and the peak inspiratory pressure（PIP）was lower than that of the control group（P＜0.05）.There was no significant difference in the incidence of adverse reactions and mortality rate between the two groups（P>0.05）.Conclusions Morphine has remarkable sedative effect in mechanical ventilation treatment of children with severe HFMD.It can quickly achieve satisfactory sedation,improve the symptoms of hypoxia in children,reduce the time of mechanical ventilation and stay in the intensive care unit,and has good safety.