Objective To explore the influential factors for long-term prognosis of diffuse axonal injury (DAI). Methods Prospective cohort study was performed on 75 patients with DAI, and related data of DAI and follow-up findings 6 months after injury were recorded. Single and multiple factor analysis were carried out to analyze the relationship between related factors and prognosis of DAI. Logistic regression analysis was employed for multiple factor analysis. Results Logistic regression analysis revealed that Glasgow coma score (GCS) score on admission (OR=0.021, 95% CI 0.007-1.557), bilateral pupillary abnormality （OR=27.532, 95% CI 8.975-57.413), number of lesions of brain central areas on diffusion weighted imaging of MRI (OR=5.753, 95% CI 2.136-9.392) and average apparent diffusion coefficient of brain central areas (OR=0.353, 95% CI 0.134-0.964) were influential factors for prognosis of DAI. The combination of the above factors provided a predictive accuracy of 92.0% for prognosis of DAI. Conclusion GCS on admission, bilateral pupillary abnormality, number of lesions of brain central areas on diffusion weighted imaging of MRI and average apparent diffusion coefficient of brain central areas are independent factors for prognosis of DAI. Accurate prognosis prediction for DAI may be provided on the basis of clinical and imaging findings.