Objective To identify molecular biomarkers associated with acute lung injury(ALI)/acute respiratory distress syndrome(ARDS)and to explore their clinical significance with public databases.Methods Two datasets GSE76293 and GSE10474 in Gene Expression Omnibus(GEO)database for ALI/ARDS gene expression chip study were used to screen genes with significant differences in both datasets.The protein-protein interaction(PPI)analysis of co-expression genes was performed based on the STRING website and Cytoscape software,and then key genes related to ALI/ARDS were identified with cytoHubba method.The ALI model was constructed using A549 cells cultured in vitro,and the expression differences of key genes in the cells were verified by RNA sequencing.Results A total of 27 up-regulated genes and 26 down-regulated genes were screened in both the two GEO datasets with Venn Diagramm.These co-expression genes were mainly involved in biological functions such as antigen processing and presentation of exogenous peptide antigen,immune receptor activity,integral component of lumenal side of endoplasmic reticulum membrane and were related to signal pathways such as antigen processing and cell differentiation.A total of 10 key genes(CD4,HLA-DQB1,CD74,HLA-DRA,FCGR2B,TOR1A,RELA,NME8,RNF19B,RHOB)related to ALI/ARDS were identified.The results of cell RNA sequencing showed that the up-regulated or down-regulated characteristics and expression differences of key genes were consistent with the results of GEO datasets.Conclusions Several key genes identified in this study may be involved in the biological process of ALI/ARDS development,and may be potential individualized molecular markers for clinical diagnosis and prognosis prediction of ALI/ARDS.