【Abstract】Objective To investigate the effects and related mechanism of rat nerve growth factor in the treatment of severe hand, foot and mouth disease complicated with central nervous system damage. Methods From February 2014 to January 2016, 120 children of severe hand, foot and mouth disease complicated with central nervous system damage hospitalized in the pediatric department of our hospital were selected and divided into observation group and control group with 60 patients in each group, accorded to the random draw envelope principle. The control group was given routine treatment. The observation group was added given the rat nerve growth factor treatment based on the control group. Results The time of disappear fever, rash and cough in the observation group were significantly less than that of the control group (P＜0.05). After treatment, the serum EV71 or CA16 antibody negative rates in the observation group were 850% and 100.0%, which were significantly higher than that of the control group (70.0% and 500%) (P＜0.05). The plasma IL-6 and CRP values in the observation group and control group after treatment were significantly less than before treatment (P＜0.05), while the plasma IL6 and CRP values of the observation group after treatment were significantly lower than the control group (P＜0.05). After treatment, the MMSE scores in the observation group and the control group after treatment were 27.56±2.25 and 20.66±3.33, which were significantly higher than that before treatment (15.26±3.21 points and 15.33±4.08)(P＜0.05). MMSE score in the observation group after treatment was significantly higher than those in control group (P＜0.05). Conclusion The rat nerve growth factor in treatment of severe hand, foot and mouth disease complicated with central nervous system damage can promote EV71 or CA16 antibody negative and have protective effects on brain function, which may be related to inhibit the expression of inflammatory cytokines.