The study finds that (i) expression levels of REEP6 are increased in tumor tissues of TSCC patients compared to that in normal tissues; (ii) high expression levels of REEP6 are related to the poor DFS of oral cancer patients with poorly differentiated tumors; (iii) REEP6 contributes to the growth, migration, drug resistance and cancer stemness in TSCC cells; (iv) a high co-expression of REEP6/EMT marker (Slug) or REEP6/stemness markers (CD166, ABCG2, ALDHA1) is related to poor DFS in oral cancer patients. Here, ABCG2 is linked to lip and oral cavity carcinoma.