Background: Various malignancies can be efficiently combated by focusing on glutathione. It is unclear how glutathione-related genes link to diffuse large B-cell lymphoma (DLBCL). Methods: Clinical information was gathered from DLBCL patients, and differences in glutathione-related differentially expressed genes (DEGs) between DLBCL and healthy groups were found. Enrichment analysis was run on the DEGs associated with glutathione. We discovered hub genes in glutathione, confirmed hub genes’ capacity for diagnosis and function prediction, and estimated drug sensitivity. Immune microenvironmental variations between healthy and DLBCL people were assessed, and hub genes for transcription factor (TF) targeting and miRNAs were found. Results: The glutathione-related DEGs were linked to biological processes such as response to oxidative stress and response to xenobiotic stimulus, according to enrichment analysis. Out of DEGs associated with glutathione, six hub genes were chosen. In the DLBCL population, there was a notable upregulation of the six hub genes. All the genes’ AUC values in the diagnostic ability category were more than 0.7, showing strong hub gene diagnostic capacity. The DLBCL population had a high level of T-cell infiltration, according to immune infiltration analysis techniques. Similar activities, such as the cell cycle G2/M phase transition and the negative control of organelle formation, are demonstrated by gene function prediction for hub. According to drug sensitivity prediction, there was a favorable link between KPNA2 with pracinostat, BRCA1 with B-7100, and LEE-011. The gene KPNA2 was shown to be concurrently targeted by many miRNAs and TFs, according to the miRNA-gene-TF interaction network. Conclusion: The relationship between DLBCL and glutathione-related genes was uncovered by our research, and six glutathione genes were linked to DLBCL. These genes might be used as diagnostic biomarkers or targets for treatment for DLBCL patients.

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