〔Abstract〕 Objective To observe the effect of intracoronary thrombolysis combined with percutaneous coronary intervention (PCI) on serum micro ribonucleic acid (miRNA) sequence and clinical indicators in patients with acute myocardial infarction (AMI). Methods The data of 74 patients with AMI admitted to Hebi People's Hospital from January 2020 to January 2023 were selected and divided into a control group and an observation group according to different treatment schemes, with 37 cases in each group. The control group was treated with PCI alone, while the observation group was treated with intracoronary thrombolysis combined with PCI. The blood flow grading, serum miRNA sequence, cardiac function indicators, and incidence of adverse reactions were compared between the two groups of patients before and after treatment. Results After treatment, the thrombolysis in myocardial infarction (TIMI) blood flow grading of the observation group was better than that of the control group, and the difference was statistically significant (P < 0.05). After treatment, the miRNA-210 and miRNA-146a levels in the observation group were lower than those of the control group, while miRNA-214 and miRNA-155 levels were higher than those of the control group, with statistically significant differences (P < 0.05). After treatment, left ventricular end diastolic volume index (LVEDVI) and left ventricular end systolic volume index (LVESVI) in the observation group were lower than those of the control group, and left ventricular ejection fractions (LVEF) levels were higher than those of the control group, with statistically significant differences (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups of patients (P > 0.05). Conclusion Intracoronary thrombolysis combined with PCI in the treatment of AMI can further regulate miRNA sequence levels, improve patient blood flow grading and cardiac function.