Objective To establish and verify the early prediction model of critical illness patients with influenza. Methods Critical illness patients with influenza who diagnosed with influenza in the emergency departments from West China Hospital of Sichuan University, Shangjin Hospital of West China Hospital of Sichuan University, and Panzhihua Central Hospital between January 1, 2017 and June 30, 2020 were selected. According to K-fold cross validation method, 70% of patients were randomly assigned to the model group, and 30% of patients were assigned to the model verification group. The patients in the model group and the model verification group were divided into the critical illness group and the non-critical illness group, respectively. Based on the modified National Early Warning Score (MEWS) and the Simplified British Thoracic Society Score (confusion, uremia, respiratory, BP, age 65 years, CRB-65 score), a critical illness influenza early prediction model was constructed and its accuracy was evaluated. Results A total of 612 patients were included. Among them, there were 427 cases in the model group and 185 cases in the model verification group. In the model group, there were 304 cases of non-critical illness and 123 cases of critical illness. In the model verification group, there were 152 cases of non-critical illness and 33 cases of critical illness. The results of binary logistic regression analysis showed that age, hypertension, the number of days between the onset of symptoms and presentation at the emergency department, consciousness state, white blood cell count, and lymphocyte count, oxygen saturation of blood were the independent risk factors for critical illness influenza. Based on these 7 risk factors, an early prediction model for critical illness influenza was established. The correct percentages of the model for non-critical illness and critical illness patients were 95.4% and 77.2%, respectively, with an overall correct prediction percentage of 90.2%. The results of the receiver operator characteristic curve showed that the sensitivity and specificity of the early prediction model for critical illness influenza in predicting critical illness patients were 0.909, 0.921, and the area under the curve and its 95% confidence interval were 0.931 (0.860, 0.999). The sensitivity, specificity, and area under the curve (0.935, 0.865, 0.942) of the early prediction model for critical illness influenza were higher than those of MEWS (0.642, 0.595, 0.536) and CRB-65 (0.628, 0.862, 0.703). Conclusions The conclusion is that age, hypertension, the number of days between the onset of symptoms and presentation at the emergency department, consciousness, oxygen saturation, white blood cell count, and absolute lymphocyte count are independent risk factors for predicting severe influenza cases. The early prediction model for critical illness patients with influenza has high accuracy in predicting severe influenza cases, and its predictive value and accuracy are superior to those of the MEWS score and CRB-65 score.