This study investigates the role of advanced glycation end-products (AGEs) in promoting hepatocellular carcinoma (HCC) progression in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). The research finds that AGEs in the extracellular matrix (ECM) increase ECM viscoelasticity, leading to enhanced collagen architecture and faster stress relaxation, but not stiffness. This viscoelasticity is linked to HCC induction, particularly when combined with oncogenic β-catenin signaling. Inhibiting AGE production, reconstituting the AGE clearance receptor AGER1, or breaking AGE-mediated collagen cross-links reduces viscoelasticity and HCC growth. Matrix analysis and computational modeling show that lower interconnectivity of AGE-bundled collagen matrix, characterized by shorter fiber length and greater heterogeneity, enhances viscoelasticity. Mechanistically, enhanced viscoelasticity promotes HCC cell proliferation and invasion through an integrin-β1-tensin-1-YAP mechanotransductive pathway. These findings reveal that AGE-mediated structural changes in the ECM can promote cancer progression in vivo, independent of stiffness.This study investigates the role of advanced glycation end-products (AGEs) in promoting hepatocellular carcinoma (HCC) progression in patients with type 2 diabetes mellitus (T2DM) and non-alcoholic steatohepatitis (NASH). The research finds that AGEs in the extracellular matrix (ECM) increase ECM viscoelasticity, leading to enhanced collagen architecture and faster stress relaxation, but not stiffness. This viscoelasticity is linked to HCC induction, particularly when combined with oncogenic β-catenin signaling. Inhibiting AGE production, reconstituting the AGE clearance receptor AGER1, or breaking AGE-mediated collagen cross-links reduces viscoelasticity and HCC growth. Matrix analysis and computational modeling show that lower interconnectivity of AGE-bundled collagen matrix, characterized by shorter fiber length and greater heterogeneity, enhances viscoelasticity. Mechanistically, enhanced viscoelasticity promotes HCC cell proliferation and invasion through an integrin-β1-tensin-1-YAP mechanotransductive pathway. These findings reveal that AGE-mediated structural changes in the ECM can promote cancer progression in vivo, independent of stiffness.