In this work, we used mouse models to (i) test whether TLR5 stimulation by entolimod can mitigate LPS and TNF toxicity in normal tissues and, if so, identify the cellular and molecular mechanisms underlying this activity, and (ii) determine whether TLR5 stimulation affects the antitumor activity of TNF in mouse hepatocellular carcinoma (HCC) and colorectal cancer (CRC) models. This evidence concerns the gene TNF and hepatocellular carcinoma.