ABSTRACT Betacoronaviruses express a small internal (I) protein that is encoded by the same subgenomic RNA (sgRNA) as the nucleocapsid (N) protein. Translation of the +1 reading frame of the N sgRNA through leaky ribosomal scanning leads to expression of the I protein. The I protein is an accessory protein reported to evade host innate immune responses during coronavirus infection. Previous studies have shown that the I proteins of severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and Middle East respiratory syndrome coronavirus suppress type I interferon production by distinct mechanisms. In this review, we summarize the current knowledge on the I proteins of betacoronaviruses from different subgenera, with emphasis on its function and role in pathogenesis.