FAM210B (family with sequence similarity 210 member B) is a novel protein that has been linked to tumor development. However, its role and underlying mechanisms in lung adenocarcinoma (LUAD) progression remain largely unexplored. In this study, FAM210B was observed to be down-regulated in LUAD cells. Analyses of public datasets revealed that decreased expression of FAM210B predicts poor survival. Accordingly, in vitro and in vivo studies have confirmed the inhibitory role of FAM210B on the growth and tumor metastasis of LUAD cells. RNA-seq analysis further indicated that FAM210B plays a role in regulating innate immune-related signaling pathways in LUAD cells, particularly involving the production of type I interferon (IFN-α/β). Specifically, FAM210B activates STAT1/IRF9/IFIT3 axis by upregulating IFN-α/β expression, leading to the inhibition of proliferation and migration of LUAD cells. Furthermore, TOM70 (Translocase of outer mitochondrial membrane 70, also named as TOMM70) has been identified as a functional interacting partner of FAM210B in its modulation on the expression of IFN-α/β, as well as the proliferative and metastatic phenotypes of LUAD cells. In conclusion, our study indicates that FAM210B is an important suppressor of cellular viability and mobility during lung cancer progression.