MicroRNAs (miRNAs) have been demonstrated to play pivotal roles in the pathogenesis of sepsis-induced acute lung injury (ALI). In this work, we aimed to clarify the potential role and the underlying mechanism of miR-942-5p in a lipopolysaccharide (LPS)-induced A549 cell injury model. The cell injury was evaluated by CCK-8 assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA). The expression levels of miR-942-5p and tripartite motif-containing protein 37 (TRIM37) were measured by real-time PCR and Western blot, and their association was then validated by bioinformatics, luciferase reporter assay and RNA pull-down assay. We found that the expression of miR-942-5p was decreased in LPS-treated A549 cells. Furthermore, LPS treatment suppressed A549 cell viability, promoted apoptosis and increased the levels of inflammatory cytokines. Conversely, overexpression of miR-942-5p increased cell viability, reduced apoptosis and alleviated inflammatory cytokine secretion in the presence of LPS. Moreover, miR-942-5p directly targeted TRIM37 by binding to the 3′-UTR of TRIM37 mRNA. Upregulation of TRIM37 effectively reversed the anti-apoptotic and anti-inflammatory effects of miR-942-5p in LPS-induced A549 cells. Our findings suggested that miR-942-5p protected against LPS-induced cell injury through inhibiting apoptosis and inflammation in A549 cells by negatively regulating TRIM37.