Objective To explore the correlation between serum inflammatory cells and electrolyte levels and the severity of hand-foot-mouth disease（HFMD）.Methods Using the Nest case-control study，we selected children hospitalized in Henan Children's Hospital from 2015 to 2019 as research objects， mapped a trend chart for comparison， and built a logistic regression model to predict the risk factors of severe HFMD.Results Multivariate logistic regression analysis showed that the increase of inflammatory cells（leukocyte， neutrophil ratio，platelet count） in the course of mild and severe HFMD（day 1 to day 3） was statistically significant（P<0.05）. The changes of electrolyte levels（increased K⁺，decreased Ca²⁺ and Na⁺） in the course of mild and severe HFMD（day 2 to day 5） was statistically significant（P<0.05）. The rate of high fever in severe HFMD group was significantly higher than that in common HFMD group（P<0.05）.Conclusion The increase of inflammatory cells（leukocyte， neutrophil ratio and platelet count） and the change of electrolyte levels（K⁺ increase，Ca²⁺ and Na⁺ decrease） can indicate the progression of severe HFMD. Monitoring the changes of inflammatory cells and electrolyte levels in peripheral blood of patients with HFMD during the course of the disease has certain clinical value. Health management of HFMD patients with high fever who live in rural areas should be strengthened.