Objective To investigate the proliferation ability and glucose metabolism of hepatocellular carcinoma (HCC) cell growth on different stiffness of matrix and to explore relevance between metabolism and biological behavior variety of HCC cells caused by matrix stiffness．Methods The influence of different stiffness of matrix on proliferation of HepG2 cell was detected by CCK-8 assay and cell count assay．2-NBDG and Flow cytometry was used to detect the effect of matrix stiffness on glucose uptake. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of Glut1. Then, 2-DG was used to inhibit glycolysis and HepG2 cells proliferation was detected. Result The proliferation ability, glucose uptake and the expression of Glut1 of HepG2 cell increased with increasing stiffness of matrix. When glycolysis was inhibited, the proliferation ability of HepG2 cell growth on different stiffness of matrix was similar. Conclusions The mechanical microenvironment has an important effect on HCC cells proliferation; stiff matrix may promote HCC cells proliferation through increasing glycolysis; this study provides the experimental basis for the clinical treatment of hepatocellular carcinoma and drug development targeting glucose metabolism.