Here, we demonstrated that there exists an important regulatory axis in tumor hypoxic microenvironment involving elevated levels of LOXL2 induced by HIF-1α; this increase results in suppression of E-cadherin suppression and activation of vimentin and the subsequent promotion of EMT and VM, both of which ultimately contribute to tumor progression in HCC. This evidence concerns the gene LOXL2 and hepatocellular carcinoma.