According to the expression levels of LOX family members in HCC cells under different stiffness stimulation and the significance role of LOX family members in pre-metastatic niche [22, 25], we speculated that the secreted LOXL2 from HCC cells might mediate the linkage between higher matrix stiffness and pre-metastatic niche, and facilitate tumor distant metastasis. In addition, higher matrix stiffness stimulation significantly altered shape and spread area of HCC cells. This evidence concerns the gene LOXL2 and hepatocellular carcinoma.