Abstract: Objective: To analyze the risk related to intensive care units (ICU) and death in children with severe hand, foot and mouth disease (HFMD) with different clinical symptoms and signs, so as to provide a reference for the identification of risk signs and various clinical outcomes in children with severe HFMD. Methods: Between 2014 and 2018, a continuous case survey was conducted on severe HFMD children of hospitalization in various counties (cities and districts) of Guangxi through on-site investigation. Epidata software was used to double input the survey data. Binary logistic regression was used to compare the odds ratio (OR) of different clinical symp-toms and signs with death and ICU admission in children with severe HFMD, and to determine which clinical symptoms and signs made children more likely to die and be admitted to ICU. Results: A total of 1,500 severe HFMD cases were investigated in various counties (cities and districts) of Guangxi from 2014 to 2018, with a male to female ratio of 1.78:1. The median age of onset was 1.85 years (range: 0-11 years). Compared with asymptomatic children, ataxia, delirium, cyanosis, gray complexion, lethargy, weakness and paralysis, limb shaking, and easy to startle were risk factors of children admitted to ICU (OR=4.924, 4.515, 2.781, 2.750, 2.311, 2.162, 2.139, and 1.361, respectively). Bloody foaming sputum, shallow shortness of breath, pale complexion, cyanosis of lips and vomiting were the risk symptoms of death (OR=19.045, 5.438, 3.175, 3.031, 2.621, respectively). Conclusion: Children with severe HFMD who have symptoms such as ataxia, delirium, and cyanosis of lips have a higher probability of further developing into critical illness and receiving intensive care. When the symptoms such as bloody frothy sputum, shallow shortness of breath, gray complexion, cyanosis of lips, and vomiting occur, attention should be paid to whether the condition worsens and leads to death.