〔Abstract〕 Objective To investigate the effect of miR-141-3p on LPS induced A549 cell injury by targeting high mobility group protein 1(HMGB1). Methods A549 cells derived from type Ⅱ alveolar epithelial cells were taken as the study object, miR-141-3p mimics, mimics NC,HMGB1gene overexpression plasmid(pcDNA3.1-HMGB1) and empty Vector were transfected into A549 cells respectively or co-transfected, then 10 μg/ml LPS was used for 24 h. Cell proliferation activity was detected by cell counting kit-8(CCK-8). The activity of lactate dehydrogenase(LDH) in the supernatant of cell culture was detected by colorimetry. The apoptosis level of each group was detected by flow cytometry. The levels of interleukin(IL)-1β, IL-6 and tumor necrosis factor α(TNF-α) were detected by enzyme-linked immunosorbent assay(Elisa). Dual luciferase reporter gene assay verified the targeted regulatory relationship between miR-141-3p andHMGB1. Results After treatment with LPS, the proliferative activity of A549 cells and the expression level of miR-141-3p decreased(P<0.05), the apoptosis rate increased(P<0.05), the levels of IL-1β, IL-6, TNF-α and the activity of LDH in supernatant increased(P<0.05). Overexpression of miR-141-3p increased the proliferation activity of A549 cells treated with LPS(P<0.05), and decreased the apoptosis rate and the levels of IL-1β, IL-6, TNF-α in cells and LDH activity in supernatant(P<0.05). However, overexpression ofHMGB1gene could reverse the ameliorative effect of miR-141-3p on LPS-induced A549 cell injury. Dual luciferase reporter gene experiment confirmed thatHMGB1was the downstream target gene of miR-141-3p. Conclusion miR-141-3p can inhibit LPS-induced apoptosis, reduce the expression level of inflammatory factors, and improve the damage of A549 cells, which may be related to the targeted regulation ofHMGB1expression.