We aimed to elucidate the roles and regulatory mechanism of miR-3188 in oxidized low-density lipoprotein (ox-LDL)-induced cell injury in THP-1 derived macrophages, thus providing a new insight for the treatment of atherosclerosis (AS). A total of 85 AS patients and 45 healthy controls were enrolled. The levels of miR-3188 and lipoprotein-associated phospholipase A2 (Lp-PLA2) in AS patients and healthy controls were detected. Then ox-LDL was used to treat human THP-1 derived macrophages. The effects of overexpression and suppression of miR-3188 on regulating ox-LDL-induced cell injury in THP-1 derived macrophages were investigated. Additionally, the potential target of miR-3188 was identified, which was verified by luciferase reporter assay. Besides, the relationship between miR-3188 and RhoA/ROCK pathway was explored. miR-3188 was downregulated in AS patients, while the levels of Lp-PLA2 in AS patients were increased. Ox-LDL significantly induced cell injury by decreasing cell viability, inducing cell apoptosis and increasing the production of inflammatory cytokines, including IL-1β, IL-6, MCP-1 and TNF-α. In addition, miR-3188 was significantly downregulated after ox-LDL treatment. Overexpression of miR-3188 alleviated ox-LDL-induced cell injury, while inhibition of miR-3188 had opposite effects. ETS-domain protein 4 (ELK4) was a target of miR-3188. The effects of miR-3188 inhibition on ox-LDL-induced cell injury were markedly reversed by knockdown of ELK4. Besides, inhibition of miR-3188 enhanced ox-LDL-activated RhoA/ROCK pathway, while knockdown of ELK4 suppressed this pathway. Downregulation of miR-3188 may contribute to AS development via negatively regulating Lp-PLA2, targeting ELK4 and activating RhoA/ROCK pathway. miR-3188 may serve as a target for AS treatment.