Background <p>Liver fibrosis (LF) is a key pathological stage in chronic liver disease that can progress to cirrhosis, hepatocellular carcinoma, and liver failure. Although both N6-methyladenosine (m6A) modification and long non-coding RNAs (lncRNAs) have emerged as important regulators of LF, whether m6A-modified lncRNAs drive LF progression remains incompletely understood.</p> Methods <p>LF-associated lncRNAs were screened from Gene Expression Omnibus datasets, and ECONEXIN was selected for further investigation. Its expression was validated by RT-qPCR in LF models. A primary hepatocyte-hepatic stellate cells (HSC) coculture system, together with functional and molecular assays, was used to examine the effects of ECONEXIN on hepatocyte pyroptosis, HSC activation, and the underlying mechanism.</p> Results <p>ECONEXIN was markedly upregulated in LF models. Functionally, ECONEXIN promoted hepatocyte pyroptosis and enhanced HSC proliferation and collagen deposition. Mechanistically, ECONEXIN acted as a competing endogenous RNA that sequestered miR-26b-5p, thereby relieving its inhibitory effect on TLR4. In parallel, METTL3-mediated m6A modification increased ECONEXIN stability and contributed to its aberrant upregulation in LF.</p> Conclusions <p>These findings define a METTL3/m6A/ECONEXIN/miR-26b-5p/TLR4 regulatory axis that drives LF progression by coupling m6A-dependent lncRNA regulation to hepatocyte pyroptosis and HSC activation. ECONEXIN may serve as a potential therapeutic target for LF.</p> Graphical Abstract <p></p>