Type Ⅰ interferons (IFN-Ⅰs) are essential for antiviral immune responses and have been developed for the treatment of various viral infections. However, the roles of IFN-Ⅰs in HIV infection remain elusive. Recent data from HIV-infected humanized mice show that IFN-Ⅰs play both protective role by suppressing HIV replication and detrimental role by inhibiting anti-HIV immune responses. Administration of IFN-Ⅰ receptor (IFNAR)blocking antibody in the presence of antiretroviral therapy (ART) rescues anti-HIV immune responses and delays HIV rebound upon the cessation of antiviral drugs. Thus，IFN-Ⅰs provide a potential target for the development of novo drugs treating HIV infection.