ObjectiveTo investigate the key long non-coding RNAs (lncRNAs) and transcription factors (TFs) in idiopathic pulmonary fibrosis (IPF) by Bioinformatics analysis.MethodsBioinformatics analysis of three gene expression profiles from the Gene Expression Omnibus dataset (GSE2052, GSE44723, and GSE24206), including 42 IPF and 21 normal lung tissues, was performed in this study. Subsequently, differentially expressed genes (DEGs) were filtered, and key genes involved in signaling pathways and the DEG-associated protein-protein interaction network (PPI) were further analyzed. The filtered genes expression was determined by real-time quantitative polymerase chain reaction analysis.ResultsA total of 8483 aberrantly expressed genes were screened, and 29 overlapping genes were identified among these three datasets. A significant enrichment analysis of DEG-associated functions and pathways was further performed. A total of 18 modules were obtained from the DEG PPI network, and most of the modules were involved in polyubiquitination, Golgi vesicle transport, endocytosis and so on. The key genes were obtained through hypergeometric testing, and most of the corresponding genes were closely associated with ubiquitin-mediated proteolysis, the spliceosome, and the cell cycle. These differential expressed genes, such as lncMALAT1, E2F1 and YBX1, were detected in the peripheral blood of IPF patients when compared with those normal control subjects.ConclusionlncMALAT1, E2F1 and YBX1 might be possible regulators for the pathogenesis of idiopathic pulmonary fibrosis.