TLR3 is a member of the toll-like receptor family that play a fundamental role in pathogen recognition and activation of the innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. TLR3 is most abundantly expressed in the placenta and pancreas. TLR3 was shown to bind to and signal the presence of double stranded RNA (dsRNA) viruses. Signaling through TLR3 can promote the NF-κB pathway to initiate innate immune responses to bacterial and viral infections, as well as the p53 pathway to trigger apoptosis of cells infected with dsRNA viruses. Therefore, TLR3 plays an important role in sensing and defending against viral infection. It has been demonstrated that positive TLR3 expression is associated with favorable histology and prognosis in neuroblastoma.