Objective. To analyze the predictive value of serum microRNA-106 (miRNA-106), miR-106, and myosin light chain 4 (MYL4) levels on the prevalence of atrial fibrillation and to explore the relationship between serum miR-106 and MYL4 and the risk stratification and prognosis of atrial fibrillation, thereby providing basis for them to become clinical targets for the treatment of atrial fibrillation in the future. Methods. 300 patients with atrial fibrillation treated in our hospital from May 2017 to March 2019 were selected as the atrial fibrillation group, and 300 healthy people who came to our hospital for physical examination in the same period were selected as the control group. The general data of the subjects in the two groups were collected. The serum miR-106 level of the subjects in the two groups was detected by fluorescence quantitative polymerase chain reaction (PCR), and the level of MYL4 was detected by enzyme-linked immunosorbent assay (ELISA). The expression of miR-106 and MYL4 in the myocardium was observed by immunohistochemistry. The relationship between the levels of serum miR-106 and MYL4 and the prevalence of atrial fibrillation and the score of atrial fibrillation thromboembolism risk stratification scoring system (cha2ds2) was compared between the two groups. The relationship between serum level of miR-106 and prognosis of patients with atrial fibrillation was analyzed. Results. The systolic blood pressure, diastolic blood pressure, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and left anterior descending artery (LAD) in the atrial fibrillation group were significantly higher than those in the control group, while HDL-C and left ventricular ejection fraction (LVEF) were significantly lower than those in the control group (P 1.96. The survival rate of patients with MYL4≥0.24 was significantly higher than that of patients with MYL4 4.5mmol/L, and that of patients with LDL-C≤2.6mmol/L was significantly higher than that of patients with LDL-C 2.6mmol/L. Conclusion. Serum miR-106 and MYL4 levels are closely related to the prevalence of atrial fibrillation, which can reflect the risk of thromboembolism in patients with atrial fibrillation and can be used as a biological indicator to predict the prognosis of patients with atrial fibrillation.