Objective To explore the correlation of MRI image and clinical outcome on damage of the central nervous system in severe hand-foot-and-mouth disease. Methods Retrospectively analyzed 42 cases of the central nervous MRI images and clinical datas of the recovery and follow-up of severe hand-foot-and-mouth patients during May 2010 and May 2013, divided these patients into positive group and negative group according to the results of the recovery image, and then compared the clinical outcomes and recover condition of the follow-up in central nerve damage of these two groups. Results There are 18 positive cases and 24 negative cases in the 42 cases MRI images; All the positive cases showed brain stem damage , in which 6 cases combined with spinal cord injury and 1 cases combined with cerebellar dentate nuclear damage. In the positive group, there were 9 cases that are clinical cure and 8 cases with nerve dysfunction, and 1 case that cannot be separated from breathing machine and transfered. In the negative group, there were 21 cases that are clinical cure and 3 cases with nerve dysfunction. The clinical cure rate of positive group was 50% (9/18), and the clinical cure rate of negative groups was 87.5% (21/24), The cure rate differences between positive group and negative group has statistically significant (p<0.05). We made the follow-up of 15 cases of positive group for 1 year, and found that there were 9 cases with lesions disappeared and 6 cases with narrowed lesions in MRI images. Conclusion After active treatment, most central nerve damage and its sequela of severe hand-foot-mouth disease were recoverable. MRI examination can be an approach for clinical judgment, but cannot predict long-term prognosis of the patients.