The coronavirus disease 2019 (COVID-19) is a global infectious disease aroused by RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients may suffer from severe respiratory failure or even die, posing a huge challenge to global public health. Retinoic acid-inducible gene I (RIG-I) is one of the major pattern recognition receptors, function to recognize RNA viruses and mediate the innate immune response. RIG-1 and melanoma differentiation-associated gene 5 contain an N-terminal caspase recruitment domain that is activated upon detection of viral RNA in the cytoplasm of virus-infected cells. Activated RIG-I and mitochondrial antiviral signaling (MAVS) protein trigger a series of corresponding immune responses such as the production of type I interferonagainst viral infection. In this review, we are summarizing the role of the structural, nonstructural, and accessory proteins from SARS-CoV-2 on the RIG-I-MAVS pathway, and exploring the potential mechanism how SARS-CoV-2 could evade the host antiviral response. We then proposed that modulation of the RIG-I-MAVS signaling pathway might be a novel and effective therapeutic strategy to against COVID-19 as well as the constantly mutating coronavirus.