Adult tethered cord syndrome (ATCS) has a hidden onset and delayed clinical symptoms. The purpose of this study is to identify hub proteins in the cerebrospinal fluid of ATCS patients through bioinformatics analysis, and to find significant heterogeneity in these proteins between ATCS patients and non ATCS patients (control group). Firstly, differential genes were screened based on proteomic results. Compared with the control group, 18 differentially expressed proteins were upregulated and 18 differentially expressed proteins were downregulated in the cerebrospinal fluid of ATCS patients. Then, GO, KEGG, and GESA functional enrichment analysis showed that ATCS patients were active in biological processes such as coagulation, inflammatory response, and regulation of humoral immune response, suggesting the possibility of spinal cord injury. In addition, protein network interaction analysis indicates that APOB, APOC3, FGA, and FGG are defined as hub proteins. The correlation between ATCS patients and immune characteristics was analyzed using the CIBERSORT algorithm, which may have generated a unique immune microenvironment. Finally, Western blotting was used to experimentally validate APOB, APOC3, FGA, and FGG. The results showed that APOB, APOC3, FGA, and FGG were upregulated in the cerebrospinal fluid of ATCS patients and had an important impact on the repair and functional maintenance of spinal cord injury. They can be used as key proteins for early and accurate diagnosis and treatment of spinal cord thrombosis syndrome, and suggest that the spinal cord of ATCS patients may be damaged, which can serve as potential therapeutic targets.