In the present study, we first indicated the role of GBP5 in progression and malignancy of OSCC as follows: (1) the expression level of GBP5 is higher in tumor tissues compared with that in normal tissues of oral cancer patients; (2) the high gene expression level of GBP5 is associated with poor prognosis in oral cancer patients with poor cell differentiation and lymph node metastasis; and (3) GBP5 plays a role in cell growth, the cell cycle, the invasion/migration, and cancer stemness of OSCC cells. Here, GBP5 is linked to cancer.