Objective: The miRNA was used to explore the molecular mechanism and effects of Panax notoginseng saponins (PNS) on coronary atherosclerosis let-7b and understand the variations in let-7b molecular mechanism after the application of PNS, which verified the therapeutic effects of PNS on coronary atherosclerosis and provided guidance for the clinical treatment and diagnosis of coronary atherosclerosis. Methods: Patients who were clinically diagnosed as coronary atherosclerosis in the hospital were taken as research objects and divided into two groups, i.e. the experiment (treatment) group, and the control group. The peripheral venous blood sample of each patient was taken in the morning on an empty stomach to extract the total RNA. In addition, patients in the two groups received symptomatic treatments, such as anti-ischemic therapy, anti-platelet therapy, and hypo-lipidemic therapy. Simultaneously, patients in the treatment group took Xuesaitong Capsule, while patients in the control group took the simulant Xuesaitong Capsule. After four weeks, blood samples were drawn again to extract the total RNA. Then, the target gene and related pathways of let-7b were determined by using the micro RNA target gene prediction software miRBase. Finally, the real-time fluorescence quantitative polymerase chain reaction (QRT-PCR) was used to investigate the effect of PNS on the molecular mechanism of coronary atherosclerosis let-7b. Results: Both let-7b and ADRB2 were up-regulated after treatment in the treatment group, while the let-7b and ADRB2 were down-regulated after treatment in the control group. In addition, the levels of molecules in the treatment group were down-regulated, including GS, AC, cAMP, PKA, and PLIN3, which indicated that PNS might regulate the downstream signaling pathway through let-7b/ADRB2 to achieve the therapeutic effects. Conclusion: The study found that the application of PNS could up-regulate let-7b and ADRB2 in patients with unstable angina pectoris, indicating that PNS functioned through let-7b and ADRB2 channels, such as protecting ischemia reperfusion of myocardial cells, mobilizing the bone marrow stem cells for angiogenesis, improving the survival rate after transplantation of bone marrow mesenchymal stem cells, reducing the apoptosis of myocardial cells, and promoting the repair of myocardial-related protein expressions. (C) 2020 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.