Interferon-gamma (IFN-gamma) plays a dual role in cancer; it is both a pro- and an antitumorigenic cytokine, depending on the type of cancer. The deregulation of the IFN-gamma canonic pathway is associated with several disorders, including vulnerability to viral infections, inflammation, and cancer progression. In particular, the interplay between lung adenocarcinoma (LUAD) and viral infections appears to exist in association with the deregulation of IFN-gamma signaling. In this mini-review, we investigated the status of the IFN-gamma signaling pathway and the expression level of its components in LUAD. Interestingly, a reduction in IFNGR1 expression seems to be associated with LUAD progression, affecting defenses against viruses such as severe acute respiratory syndrome coronavirus 2. In addition, alterations in the expression of IFNGR1 may inhibit the antiproliferative action of IFN-gamma signaling in LUAD.