gC1qR is one of the C1q receptors implicated in the regulation of innate and adaptive immunity. We found that gC1qR inhibits RIG-I and MDA5-dependent antiviral signaling. Double stranded RNA and virus trigger the translocation of gC1qR to the mitochondrial outer membrane leading to the interaction of gC1qR with the RIG-I and MDA5 adaptor, VISA/MAVS/IPS-1/Cardif. The interaction of gC1qR with VISA/MAVS/IPS-1/Cardif at mitochondria results in the disruption of RIG-I and MDA5 signaling and the promotion of virus replication. Knockdown of endogenous gC1qR enhances RIG-I-dependent antiviral signaling, and augments the inhibition of virus proliferation. Therefore, gC1qR is a physiological inhibitor of the RIG-I and MDA5-mediated antiviral signaling pathway. These data uncover a new viral mechanism used to negatively control antiviral signaling in host cells.