Intestinal microbiota and TLR4 are significant factors in Hepatocellular carcinoma. They promote cancer cell proliferation and reduce HBV replication. Wu et al. showed that TLR3 or TLR4-activated Kupffer cells combined with TLR3-activated LSECs led to soluble-molecule-dependent reduction of HBV replication in vitro. The gene discussed is TLR3; the disease is cancer.