Recent great progress in studies of innate immunity has revealed that an array of pattern recognition receptors (PRRs) are involved in the detection of microbes to activate innate responses. In particular, during viral infection, virus-derived nucleic acids serve as major microbe–associated molecular patterns (MAMPs), which are sensed by certain PRRs, leading to the activation of their downstream signaling pathways. In most cases, such viral sensors induce interferon (IFN) gene activation to trigger antiviral activity. We recently identified RIG-I (retinoic acid-inducible gene-I), which is known to be a cytoplasmic RNA sensor for RNA virus infection, as an innate sensor for hepatitis B virus (HBV) infection in human hepatocytes. The 5’-epsilon region of HBV pregenomic RNA (pgRNA) was shown to be a target region for the RIG-I-mediated sensing. In addition, we also found a new aspect of RIG-I as an antiviral factor that directly inhibits HBV replication. On the other hand, we have recently found a novel regulatory mechanism for viral sensor-mediated IFN pathway. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-inducible poly(ADP-ribose)polymerase (TIPARP) was shown to be a key mediator to negatively regulate IFN production activated by nucleic acid innate sensors such as RIG-I. We also found that the TIPARP-mediated regulation of IFN production was based on constitutive activation of aryl hydrocarbon receptor (AHR) mediated by endogenous ligands such as kynurenine, one of the tryptophan metabolites. Our results suggest that the AHR-TIPARP axis may represent a potential therapeutic target for the control of viral infection.