Objective：To investigate the effects of DIX domain-containing protein 1 (Dixdc1) on the proliferation, migration, and polarization of astrocytes following traumatic brain injury (TBI) in mice. Methods：A mouse model of traumatic brain injury was established using the controlled cortical impact (CCI) device. Western blotting was employed to examine the expression changes of Dixdc1, glial fibrillary acidic protein (GFAP), the neurotoxic astrocyte marker complement 3 (C3), and the neuroprotective astrocyte marker S100 calcium-binding protein A10 (S100A10) before and after injury. Immunohistochemical staining was performed to observe the expression and distribution of Dixdc1 and GFAP, while immunofluorescence staining was used to assess the colocalization of Dixdc1 with GFAP. Short hairpin RNA (shRNA) was utilized to knock down Dixdc1 levels in astrocytes. Lipopolysaccharide (LPS) stimulation was then applied to mimic the activated state of astrocytes in vitro. Western blotting was conducted to detect expression changes of Dixdc1, GFAP, C3, S100A10, as well as cell proliferation and migration-related proteins. Flow cytometry was performed to analyze the cell cycle, accompanied by Western blot detection of S-phase-related proteins. RT-PCR was used to measure the expression of astrocyte phenotype polarization markers. Cellular immunofluorescence was employed to detect the fluorescence intensity of C3 and S100A10. Additionally, Western blotting was performed to assess the phosphorylation level of signal transducer and activator of transcription 3 (STAT3). Result：Compared with the Sham group, the protein expression levels of Dixdc1 and GFAP were upregulated in the cerebral cortex of TBI mice. Dixdc1 was expressed in astrocytes within the peri-lesional cortical regions. Following LPS stimulation, the protein expression levels of both Dixdc1 and GFAP were upregulated in C8-D1A cells. Scratch assay and EdU assay demonstrated that knockdown of Dixdc1 suppressed LPS-induced astrocyte proliferation and migration, downregulated the expression of associated proteins, reduced the proportion of cells in the S phase of the cell cycle, and decreased CyclinA and CDK2 protein levels. C3 showed elevated expression levels during the acute phase but declined thereafter, whereas S100A10 demonstrated an inverse temporal pattern. Dixdc1 knockdown inhibited LPS-induced A1-type astrocyte polarization by reducing STAT3 phosphorylation levels, which concurrently downregulated C3 protein expression and upregulated S100A10 protein expression. Conclusion：Following traumatic brain injury, Dixdc1 protein expression was upregulated in astrocytes. Knockdown of Dixdc1 markedly suppressed LPS-induced proliferation, migration, cell cycle and STAT3 phosphorylation of A1-type astrocytes.