Objective To explore the risk factors of poor prognosis of moderate and severe traumatic brain injury (TBI) in preschool children. Methods From January 2015 to December 2020，245 preschool children with moderate and severe TBI were treated in the Department of Neurosurgery of the Affiliated Hospital of Guizhou Medical University. The average follow-up time was （37.17±18.10） months. According to the Glasgow outcome scale (GOS)，the children were divided into two groups: good prognosis group (n=189) and poor prognosis group (n=56). Independent prognostic risk factors were analyzed by multivariate 〖JP2〗Logistic regression. Results The results of univariate analysis showed that there were significant differences between the two groups in chief complaint，injury mechanism，GCS，Rotterdam CT score，brainstem injury，combined injury，infection，complications，serum calcium and albumin at the first time，abnormal blood coagulation and so on. Logistic regression analysis showed that brainstem injury，admission GCS，complications and serum calcium for the first time were risk factors for poor prognosis. Conclusion The poor prognosis of moderate and severe TBI in preschool children is affected by many risk factors. Brain stem injury，GCS<9，complications during hospitalization and the first down-regulation of serum calcium are the risk factors for poor prognosis.