Objective  To investigate the changes and significance of serum Monocyte chemoattractant protein-1 (MCP-1), Vasohibin-1 (VASH-1) and Nicotinamide adenine dinucleotide phosphatase oxidase 4 (NOX4) levels in maintenance hemodialysis patients.  Methods A total of 240 patients with stage 5 chronic kidney disease admitted to Hefei Hospital Affiliated to Anhui Medical University from March 2022 to February 2024 were selected. All patients were treated with maintenance hemodialysis. Serum MCP-1, VASH-1 and NOX4 were measured before the first dialysis and three months after dialysis. According to the prognosis of patients, they were divided into poor prognosis group and good prognosis group. The general data and serum MCP-1, VASH-1 and NOX4 levels before the first dialysis and three months after dialysis were compared between the two groups. Logistic regression analysis was used to analyze the prognostic factors of maintenance hemodialysis patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of MCP-1, VASH-1 and NOX4 difference in the prognosis of CKD maintenance hemodialysis patients.  Results  A total of 240 maintenance hemodialysis patients were followed up for 1 year, and 6 patients were lost to follow-up, a total of 234 patients were followed up, of which 50 patients had poor prognosis, accounting for 21.37%, and were included in the poor prognosis group, the remaining 184 patients were included in the good prognosis group. After three months of dialysis, the levels of serum MCP-1, VASH-1 and NOX4 of patients in the poor prognosis group and the good prognosis group were significantly higher than those before the first dialysis, and the levels and differences of serum MCP-1, VASH-1 and NOX4 in the poor prognosis group were higher than those in the good prognosis group (t=7.384, 12.974, 6.409, 12.638, 5.415, 12.296, all P<0.001); multivariate. After adjusting for diabetes mellitus and albumin, △MCP-1 (OR=1.332,95%CI: 1.106-1.605, P<0.001), △VASH-1 (OR= 1.383,95%CI:1.132-1.689, P<0.001), △ NOX4 (OR=1.313,95%CI:1.061-1.626, P<0.001) were still independently associated with the prognosis of patients with CKD maintenance hemodialysis (P<0.05). The ROC curve showed that the area under the curve (AUC) value of △MCP-1, △VASH-1 and △NOX4 combined to predict the prognosis of maintenance hemodialysis patients was 0.869, which was significantly greater than that of each index alone (Zcombined-△MCP-1= 2.497, Pcombined-△MCP-1< 0.001; Zcombined-△VASH = 2.566, Pcombined-△MCP-1<0.001; Z combined-△NOX4= 2.842, P combined-△MCP-1<0.001).  Conclusion  The levels of serum MCP-1, VASH-1 and NOX4 in patients with maintenance hemodialysis are significantly increased, and the difference is closely related to the prognosis and survival. The combined prediction of △MCP-1, △VASH-1 and △NOX4 has higher prognostic efficacy, which is helpful for early clinical identification of high-risk patients and timely optimization and adjustment of dialysis strategies.