Laryngeal papillomas (LP) is a difficult disease to manage due to its frequent recurrence, airway compromise, and risk of cancer. Recently, growing evidence indicates the aberrant expression of OGFPD1, a stress granule protein, links closely to the development of tumorigenesis; however, little is known about its role in LP progression. Here, we investigated the tumor promoting action of OGFOD1 in LP. The transcriptional and translational levels of OGFOD1 were significantly up-regulated in LP tissues and cells. Moreover, OGFOD1 promoted viability and proliferation, and inhibited LP cells apoptosis. We further revealed that OGFOD1 was directly targeted by miR-1224-5p, which was significantly down-regulated in LP. Overexpression of the miR-1224-5p suppressed OGFOD1-induced cell proliferation and viability, and promoted apoptosis of LP. In accordance, knockdown of miR-1224-5p inversed the inhibitory effects. In confederation of the central involvement of OGFOD1 in LP progression, targeting the miR-1224-5p/OGFOD1 pathway might provide a novel strategy for LP treatment.