Update publication information. Chronic mountain sickness (CMS) is a progressive incapacitating syndrome induced by lifelong exposure to hypoxia. In the present study, proteomic analysis was used to identify the differential expression proteins (DEPs) and then evaluate the potential biomarkers between CMS and non-CMS groups. A total of 145 DEPs were detected among CMS Han Chinese people who live in the plateau (CMS-HPu), among which 89 were significantly upregulated and 56 were significantly downregulated. GO enrichment analysis showed that various biological processes were enriched, including the hydrogen peroxide metabolic/catabolic process and reactive oxygen species (ROS) metabolic and acute inflammatory response. Protein–protein interaction analysis showed that antioxidant activity, the hydrogen peroxide catabolic process, and peroxidase activity were primarily mapped in interaction proteins. Nine modules showed significant clustering based on WGCNA analysis, with two being the most significant, and GO analysis showed that proteins of both modules were primarily enriched in oxidative stress-related biological processes. Four DEPs whose activities were increased in CMS patients were evaluated as the candidate biomarkers, especially the hemoglobin beta chain (HB-β), thioredoxin-1 (TRX1), and phosphoglycerate kinase 1 (PGK1). This study provides novel insights into the pathogenesis of CMS and further evaluates the potential biomarkers for its prevention and treatment.