Aim To evaluate the prognostic value of plasma interleukin-6 (IL-6) and interleukin-27 (IL-27) level in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Methods Patients with STEMI diagnosed first time and underwent PCI in People’s Hospital of Xinjiang Uygur Autonomous Region were consecutively enrolled from January 2015 to December 2016. Clinical data and blood samples before PCI were obtained from all patients. Plasma levels of IL-6 and IL-27 were measured by enzyme-linked immunosorbent assay. The patients were divided into two groups based on the occurrence of major adverse cardiovascular events (MACE) during 1-year follow-up after STEMI diagnosis. Logistic regression analysis was performed to evaluate the relationship between plasma IL-6 and IL-27 levels and the occurrence of MACE. The receiver operating characteristic (ROC) curve was applied to evaluate the predictive values of IL-6 and IL-27 on the occurrence of MACE. Results Among 287 patients with STEMI, 179 (62.4%) were males and the age was 61.37±9.3,7 (19.9%) had MACE. Compared with controls, patients in MACE group were older with higher Gensini score, higher plasma IL-6 and IL-27 levels. The prevalence of smoking, diabetes, and two- or multi-vessel coronary artery disease were higher in MACE group in comparison to controls. Logistic regression analysis demonstrated that IL-6 (OR＝1.2,5%CI was 1.50～2.15, P＜0.001) and IL-27 (OR＝1.4,5%CI was 1.11～1.42, P＜0.001) were significantly independent predictors of MACE in STEMI patients undergoing PCI. The area under the ROC curve of IL-6 and IL-27 for predicting MACE were 0.701 and 0.690, respectively. Conclusion Plasma IL-6 and IL-27 levels were independent risk predictors for identifying the MACE of 1-year follow-up in patients with STEMI underwent PCI, indicating that they may help to assess the clinical outcomes for us.