〔Abstract〕 Objective To investigate the role of lncSIL in transforming growth factor-β1(TGF-β1)-induced alveolar epithelial interstitial transformation(EMT) and its related signaling pathways. Methods Western blot was used to detect the effect of lncSIL silencing on the expression of E-cadherin(E-cad), alpha-smooth muscle actin(α-SMA) and Collagen I(Col I) in the process of EMT induced by TGF-β1. LncSIL interacting proteins were analyzed by RNA pulldown. Western blot was used to detect the effect of overexpression or silencing of lncSIL on the expression of its target gene enhancer of zeste homolog 2(EZH2) and its downstream factors P21 and cyclin-dependent kinase 6(CDK6). Flow cytometry was used to analyze the effect of lncSIL on cell cycle progression. Results After lncSIL silencing, the expression of α-SMA and Col I increased, the expression of E-cad decreased. RNA pulldown assay showed that EZH2 was the target protein that interacted with lncSIL, and the expression of EZH2 increased after silencing lncSIL, the expression of EZH2 downstream gene P21 decreased, CDK6 increased. Flow cytometry showed that the number of cells in S phase significantly increased. When lncSIL was overexpressed, the expression of EZH2 and CDK6 was down-regulated, the expression of P21 was up-regulated, and the number of S phase cells significantly decreased. Conclusion LncSIL inhibits TGF-β1-induced alveolar epithelial cell mesenchymal transition by negatively regulating EZH2/P21/CDK6 signaling pathway to inhibit cell cycle progression.