To observe the functional differences in the key brain areas in patients with different levels of consciousness after severe brain injury, and provide reference for confirming the objective diagnosis indicators for prolonged disorders of consciousness (pDoCs).This prospective study enrolled patients with pDoCs hospitalized in the department of rehabilitation medicine of our Hospital. Levels of consciousness and clinical outcomes were assessed according to diagnostic criteria and behavioral scales. Resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) of 30 patients with different levels of consciousness was performed. The patients were grouped as conscious or unconscious according to whether they regained consciousness during the 12-month follow-up.Thirty patients were enrolled, including eight with unresponsive wakefulness syndrome/vegetative state, eight with minimally conscious state, six with emergence from the minimally conscious state, and eight with a locked-in syndrome. There were 19 and 11 patients in the conscious and unconscious groups. Compared with the unconscious group, the left basal nucleus was activated in the conscious group, and there were significant differences in white matter fiber bundles. Correlations were observed between the regional homogeneity (ReHo) value of the cerebellum and the Glasgow coma scale score (r = 0.387, P = 0.038) and between the ReHo value of the left temporal and the coma recovery scale-revised score (r = 0.394, P = 0.035).The left insula and cerebellum might be important for regaining consciousness. The brain function activity and structural remodeling of the key brain regions and the activation level of the cerebellum are correlated with clinical behaviors and have potential application value for the prognosis prediction of pDoCs patients.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.