Abstract: Upper respiratory tract is directly connected with the external environment， and its natural immune system is the first line of defense against pathogens. In antiviral infection， interferon （IFN） is the main component of the antiviral natural immune system and IFN-λ is a newly discovered immune effector molecule that is mainly produced in the mucosal barrier. IFN-λ exerts a biological role through Janus kinase （JAK） and signal transducer and activator of transcription （STAT） signaling pathway， and plays an important part in regulating innate and acquired immunity of respiratory mucosa. IFN-λ principally expresses on the mucosal barrier with a long-lasting antiviral impact and controls immune-inflammatory damage， which is becoming a new focus of antiviral immunity research in the upper respiratory tract， especially in fighting against 2019 novel coronavirus diseases （COVID-19）. Thus， we summarize the research progress of IFN-λ antiviral immunity in the upper respiratory tract to provide new insight in the prevention and treatment of viral infection in the upper respiratory tract.