The Coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To facilitate its own replication and avoid immune control, SARS-CoV-2 manipulates its target cells. Our results revealed that the SARS-CoV-2 non-structural protein 1 (Nsp1) plays a key role in viral immune evasion. It blocks the mRNA tunnel of the cellular ribosome, resulting in a shutdown of translation and strong attenuation of the host's antiviral immune response.