Background <p>Acute coronary syndrome (ACS) is a common emergency in the cardiovascular system. The prevention, diagnosis, and treatment of ACS are critical and continuous issues in the clinic. Identifying non-invasive and promising biomarkers for ACS is of great clinical significance. This study evaluated the significance of miR-885-5p in the early screening, severity evaluation, and prognosis prediction of ACS, aiming to explore novel biomarkers for its clinical management.</p> Methods <p>Serum miR-885-5p levels were compared between 134 ACS patients and 122 non-ACS patients. The clinical significance of miR-885-5p was assessed from the perspectives of discriminating ACS patients, risk prediction, severity evaluation, and prognosis prediction. In vitro, the ox-LDL-induced HCAEC models were employed, and the regulatory effects of miR-885-5p on cell viability, inflammation, oxidative stress, and endothelial function were estimated. The regulatory mechanism was explored, focusing on the involvement of FBXO28.</p> Results <p>Increasing serum miR-885-5p could discriminate ACS patients and predict onset risk. miR-885-5p was positively correlated with myocardial injury-, severity-, and endothelial dysfunction-related clinicopathological features and could predict the risk of MACEs in ACS patients. In HCAECs, ox-LDL induced significant upregulation of miR-885-5p, suppressed cell viability, enhanced inflammation, promoted oxidative stress, and induced endothelial injury. Silencing miR-885-5p could protect HCAECs from ox-LDL-induced injury. FBXO28 was predicted as a direct target of miR-885-5p, negatively regulated by miR-885-5p. The knockdown of FBXO28 could reverse the protective effect of miR-885-5p silencing.</p> Conclusions <p>Circulating miR-885-5p served as a biomarker for the diagnosis and prognosis of ACS. Silencing miR-885-5p could alleviate ox-LDL-induced endothelial cell injury by targeting FBXO28.</p>