Objective To investigate the impact of GSR on the metabolism of malignant colorectal tumors and its prognostic value for patients with colorectal cancer.Methods Differential proteomics was used to obtain differentially-expressed proteins between colorectal cancer tissues and normal colon epithelial tissues.Key proteins in metabolic path-ways were identified through enrichment analysis and protein-protein interaction(PPI)network analysis,followed by survival analysis and clinical correlation analysis.Tissue microarray chips were created from surgical pathological speci-mens of 120 patients with colorectal cancer and immunohistochemical staining was performed.Results Differential pro-teomics analysis identified a total of 1 209 differentially-expressed proteins.KEGG enrichment analysis revealed that these proteins were significantly enriched in metabolic pathways,with a total of 144 enriched proteins.PPI analysis indi-cated that ADH1A,ADH1B,ADH1C,ADH5,ALDH18A1,ALDH3A1,GSTA1,GSTA2,HPGDS,GSR were key pro-teins in the metabolic pathway of differentially-expressed proteins in colorectal cancer.Survival analysis via GEPIA2 re-vealed that GSR influences the overall survival time of patients with colorectal cancer(P=0.0017,HR=0.45).Analy-sis from the UALCAN database revealed that patients with high GSR expression had lower N-stage,overall stage,and a lower TP53 mutation rate.Immunohistochemical results from the tissue microarray chip showed that GSR expressed highest in normal colon epithelial tissue,lowest in colorectal cancer tissues with combined liver metastasis,and interme-diate in colorectal cancer tissues without combined liver metastasis,with significant differences among the three groups.Conclusion GSR may influence tumor metabolism,staging,TP53 mutation,and the prognosis of patients with malig-nant colorectal tumors.