Treatment of Hep3B, HepG2 cells, and patient-derived 3D organoids with recombinant FSTL1 or conditioned medium collected from HSCs or cells overexpressing FSTL1 promoted HCC growth and metastasis by binding to the TLR4 receptor and activating AKT/mammalian target of rapamycin (mTOR)/4E-binding protein 1 (4EBP1) signaling. Here, FSTL1 is linked to hepatocellular carcinoma.