In the present study, we provide evidence that LPS-induced TLR4 signaling promotes HCC cell invasion and EMT in vitro and in vivo, and a high expression of TLR4 in HCC tissues was strongly associated with both poor cancer-free survival and overall survival in patients, which indicates that LPS is closely related to tumor invasion and metastasis, rather than only anti-tumor effects. This evidence concerns the gene TLR4 and hepatocellular carcinoma.