Aim To investigate the changes of lncRNA-ZFAS1/Caspase-3 axis in patients with ST-segment elevation myocardial infarction(STEMI) and its relationship with prognosis of emergency percutaneous coronary intervention(PCI). Methods STEMI patients who received emergency PCI were selected as STEMI group, and the healthy volunteers during the same period were selected as control group. The expression level of lncRNA-ZFAS1 in peripheral blood and the content of Caspase-3 in serum were detected. The occurrence of major adverse cardiovascular events(MACE) of STEMI patients within 6 months after PCI was followed up. Kaplan-Meier curve was used to analyze the difference of MACE in patients with different levels of lncRNA-ZFAS1 expression in STEMI group, ROC curve was used to analyze the predictive value of lncRNA-ZFAS1 for MACE in STEMI patients, Logistic regression model was used to analyze the influencing factors of MACE in STEMI patients. Results The expression level of lncRNA-ZFAS1 in peripheral blood and serum content of Caspase-3 in STEMI group were higher than those in the control group (P＜0.05), and lncRNA-ZFAS1 was positively correlated with Caspase-3. The cumulative incidence of MACE in patients with high lncRNA-ZFAS1 expression was higher than that in patients with low lncRNA-ZFAS1 expression in STEMI group, lncRNA-ZFAS1 expression had predictive value for MACE in STEMI group. cTnI peak value, multi vessel disease, and time from onset to PCI, Gensini score, lncRNA-ZFAS1 and Caspase-3 were the influencing factors of MACE in STEMI patients. Conclusion The lncRNA-ZFAS1/Caspase-3 axis was significantly changed in STEMI, and lncRNA-ZFAS1 expression level and Caspase-3 content were increased, which were related to MACE after PCI.