Hepatocellular carcinoma (HCC) is a malignant disease that seriously endangers human health. The stiffness of the extracellular matrix (ECM) in liver is increasing in the occurrence and development of HCC. In recent years, studies on the role of biomechanical factors in HCC have shown that the increase of ECM stiffness plays an important role in the occurrence and development of HCC. This article mainly reviewed the changes of ECM stiffness as well as the causes of such changes in the occurrence and development of HCC, and the effect of increased ECM stiffness on HCC-associated cells and the mechanotransduction therein, so as to provide new ideas and directions for the clinical treatment of HCC.