Objective To compare the clinical effect of different doses of methylprednisolone in the treatment of children with severe hand foot mouth disease research and analysis. Methods 100 patients in our hospital from January 2014 to August 2016 were selected and randomly divided into the control group and the experimental group, with 50 patients in each group. The control group were treated with small doses of methylprednisolone, 2 mg/ (kg?d), intravenous injection. The experimental group was treated with large dose of methylprednisolone, 10～15 mg/(kg?d) intravenous infusion. The therapeutic effects of the experimental group and the control group were compared and analyzed. Results after the corresponding treatment, the number of adverse reactions in the experimental group was 31, the adverse reaction rate was 62.0％, and the adverse reaction rate in the control group was 60.0％. There was no significant difference in the incidence of adverse reactions between the two groups. The upper respiratory rate and critical illness in the experimental group were 26.0％ and 32.0％, significantly lower than that of the control group (P<0.05). The average remission time of the patients in the experimental group was (2.19±1.01) days. The symptomatic remission time in the control group was (4.19±1.89) days. The remission time of the control group was significantly longer than that of the experimental group, with statistical difference (P<0.05). Conclusion The short term large dose of methylprednisolone in treatment of children with severe HFMD clinical effect is ideal, can be reduced to critical illness rate, less symptom remission time, with the further promotion of the clinical significance.