In epithelial cells, Scribble forms cell-cell junctions and contributes to cell morphology and homeostasis by regulating apical-basolateral polarity in mammals and functions as a tumor suppressor in many carcinomas. The initial diagnosis of oral squamous cell carcinoma is important, and its prognosis is poor when accompanied by metastasis. However, research on the mechanisms of oral squamous cell carcinoma metastasis is insufficient. Herein, we showed that Scribble regulates the apical-basolateral polarity of oral squamous cell carcinoma by regulating lethal giant larvae 1, Scribble module and E-cadherin, the adhesion junction. The expression of lethal giant larvae 1 and E-cadherin decreased when the expression of Scribble was knocked down and their localization was completely disrupted in both the oral squamous cell carcinoma cell line and model. In particular, the Scribble was involved in oral squamous cell carcinoma metastasis via hsa-miR-199b-5p, which is a microenvironmental factor of hypoxia. The disruption of Scribble localization under hypoxic conditions, but its localization was maintained in miR-199b-5p oral squamous cell carcinoma cell lines and . These results suggest that Scribble functions as a tumor suppressor marker mediated by miR-199b-5p in oral squamous cell carcinoma.