Long non-coding RNAs (lncRNAs) play an important role in various physiological and pathological processes. However, the biological role of lncRNA Meg8 in liver fibrosis is largely unknown. In this study, we found that Meg8 was over-expressed in activated hepatic stellate cells (HSCs), injured hepatocytes (HCs) and fibrotic livers. Furthermore, we revealed that Meg8 suppressed the expression of the pro-fibrogenic and proliferation genes in activated HSCs. In addition, silencing Meg8 significantly inhibited the expression of the epithelial markers, while noticeably promoted the expression of the mesenchymal markers in primary HCs and AML12 cells. Mechanistically, we demonstrated that Meg8 suppressed HSCs activation and epithelial-mesenchymal transition (EMT) of HCs through inhibiting the Notch pathway. In conclusion, our findings indicate that Meg8 may serve as a novel protective molecule and a potential therapeutic target of liver fibrosis. • Meg8 is over-expressed in activated HSCs, injured HCs and fibrotic liver. • Meg8 suppresses pro-fibrogenic and proliferation genes expression, thus inhibiting HSCs activation. • Silencing Meg8 significantly promotes EMT of primary HCs and AML12 cells. • Meg8 suppresses HSCs activation and HCs EMT through inhibiting the Notch pathway. [ABSTRACT FROM AUTHOR]