Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic parenchymal lung disease of unknown etiology and lacks an effective intervention. Long noncoding RNAs (lncRNAs) participate in organ fibrosis and various pulmonary diseases, but the role of lncRNAs in lung fibrosis is not fully understood. In the present study, we identified that lncRNA NONMMUT021928, designated as pulmonary fibrosis-associated lncRNA (PFAL), was up-regulated in the lungs of mice with experimental lung fibrosis, and in TGF-β1-induced fibrotic lung fibroblasts. Further study showed that overexpression of PFAL promoted cell proliferation, migration, and fibroblast-myofibroblast transition. Overexpression further resulted in extracellular matrix deposition and fibrogenesis in lung fibroblasts through regulation of microRNA-18a (miR-18a). Importantly, knockdown of PFAL alleviated lung fibrosis both in vitro and in vivo. Mechanistically, our study showed that PFAL promoted lung-fibroblast activation and fibrogenesis by acting as a competing endogenous RNA for miR-18a: forced expression of PFAL inhibited the expression and activity of miR-18a, whereas silencing of PFAL had the opposite effect. Furthermore, we found that miR-18a was decreased during lung fibrosis in vitro and in vivo, as well as in patients with IPF. Moreover, knockdown of miR-18a led to fibrogenesis in lung fibroblasts, whereas enhanced expression of miR-18a attenuated TGF-β1-induced lung fibrosis by directly targeting the regulation of connecting tissue growth factor. Taken together, these results revealed the effect and mechanism of lncRNA PFAL in pulmonary fibrosis and suggested that PFAL depletion may provide a novel strategy for the treatment of lung fibrosis.-Li, X., Yu, T., Shan, H., Jiang, H., Sun, J., Zhao, X., Su, W., Yang, L., Shan, H., Liang, H. lncRNA PFAL promotes lung fibrosis through CTGF by competitively binding miR-18a.