microRNA (miRNA) had been found played an important role in occurrence and development of acute myocardial infarction (AMI) disease. In this paper, we found that the circulating miR-223-3p in AMI patients was significantly higher than that in unstable angina (UA) patients and healthy people. Univariate and logistic regression analysis showed the circulating miR-223-3p was a protective factor in the occurrence of AMI. We also found that the circulating miR-223-3p was negatively correlated with the serum CK-MB, cTnI, AST, LDH, TNF-α, IL-6, IL-1β and IL-8. The luciferase reporter gene system confirmed that miR-223-3p targeted inhibition of NLRP3 expression in THP-1 and human peripheral blood mononuclear cell (PBMC), and miR-223-3p was negatively correlated with the expression of NLRP3 in the PBMC of AMI patients. In PBMC of healthy people, miR-146a-mimic could increase the expression of NLRP3, but decreased the level of TNF-α secretion. Moreover, H2C9 cells apoptosis by TNF-α in a dose-dependent. In conclusion, these results suggested that miR-223-3p suppressed inflammation to protect cardiomyocytes by targeting NLRP3 in AMI patients.