Objective  To investigate the relationship between serum microRNA (miR)-222 and miR-150 expression and major adverse cardiovascular events (MACE) in patients undergoing maintenance hemodialysis (MHD).  Methods  A total of 284 MHD patients admitted to the First Hospital of Baoding from March 2020 to March 2023 were enrolled and followed up for 2 years. Patients were divided into the MACE group (n=93) and non-MACE group (n=191) according to the occurrence of MACE. Serum miR-222 and miR-150 levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Pearson correlation analysis was used to examine the correlation with clinical data. Multivariate Cox regression analysis was performed to identify influencing factors of MACE. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive value of the two microRNAs.  Results  Age, dialysis vintage, troponin, and myoglobin were higher in the MACE group than in the non‑MACE group (t=3.716, 6.214, 9.330, 8.048, all P<0.001), while hemoglobin, miR-222, and miR-150 were lower (t=7.097, 9.833, 9.257, all P<0.001). Pearson analysis showed that miR-222 was negatively correlated with age, dialysis vintage, troponin, and myoglobin (r=–0.432, –0.426, –0.622, –0.593, all P<0.001) and positively correlated with hemoglobin (r=0.552, P<0.001). miR-150 was negatively correlated with age, dialysis vintage, troponin, and myoglobin (r=–0.403,       –0.384, –0.618, –0.581, all P<0.001) and positively correlated with hemoglobin (r=0.522, P<0.001). Multivariate COX regression showed that age (HR=1.262, 95% CI: 1.048～1.520, P=0.014), dialysis vintage (HR=1.458, 95% CI: 1.099～1.933, P=0.009), hemoglobin (HR=0.579, 95% CI: 0.373～0.898, P=0.015), troponin (HR=2.026, 95% CI: 1.266～3.243, P=0.003), myoglobin (HR=2.522, 95% CI: 1.533～4.149, P<0.001), miR-222 (HR=0.446, 95% CI: 0.285～0.699, P=0.001), and miR-150 (HR=0.536, 95% CI: 0.388～0.741, P<0.001) were influencing factors for MACE. The ROC curve showed that the area under the curve (AUC) of combined detection for predicting MACE was 0.913 (95% CI: 0.880～0.945), which was significantly higher than that of each alone (miR-222: Z=2.482, P=0.013; miR-150: Z=3.109, P=0.002).  Conclusion  Low serum expression of miR-222 and miR-150 is associated with an increased risk of MACE in MHD patients, and the combined detection has high predictive efficacy.