Objective To determine the expression profile of microRNAs (miRNAs) in the patients with unstable coronary heart disease and investigate the regulation role of differential expressed miRNAs in cell proliferation. Methods (1) After the plasma samples of patients with confirmed unstable coronary heart disease and non-coronary heart disease with suspected angina (control) were collected, miRNAs array was employed to identify distinct miRNA expression profiles. (2) The potential target genes of the above miRNAs were predicted by 3 miRNA target prediction algorithms, TargetScan, miRanda and DIANAmT. (3) The genes predicted by the three algorithms were further analyzed for their regulation roles in cell proliferation and involed signaling pathways by DAVID database. (4) Real-time PCR were used to test plasma miR-19b levels in patients with unstable coronary heart disease compared with the controls. (5) Based on the results of function cluster analysis, the effect of the most differentially expressed miR-19b was detected on the regulation of cell proliferation. Results (1) Compared with the controls, there were 39 differentially expressed miRNAs, and miR-19b was the most obviously one. (2) By analyzing the target genes of the differential expressed miRNAs, there were 14 miRNAs closely related with cell proliferation, and miR-19b was the closest one. (3) Real-time PCR confirmed that the plasma miR-19b level was obviously higher in the patients with unstable coronary heart disease than in the controls. (4) The results of CCK-8 assay showed that miR-19b indeed inhibited the proliferation in EA.hy926 cells. Conclusion There is a specific expression profile of circulating miRNAs in the patients with unstable coronary artery disease. The differentially expressed miRNAs may be the biomarkers of unstable coronary heart disease. MiR-19b may play a protective role in the stability of atherosclerotic plaque by inhibiting the proliferation of endothelial cells.