Overexpression of epidermal growth factor receptor (EGFR) is associated with resistance to chemotherapy and radiotherapy, advanced tumor stage, invasion, metastasis and poor prognosis in malignant tumors. EGFR, therefore, has been an attractive molecular target for chemotherapy. However, the results of clinical studies using inhibitors of its kinase activity have not been promising because the response rates were at most 20%. Sodium-glucose co-transporter 1 (SGLT1) is a membrane protein that mediates the transport of glucose across cellular membranes. EGFR physically associates with and stabilizes SGLT1 to promote glucose uptake into cancer cells through a kinase-independent process. The purpose of this study was to investigate the coexpression of SGLT1 and EGFR and its relationships with clinicopathological features in oral squamous cell carcinoma (OSCC). SGLT1 and EGFR were detected in all OSCC cell lines, and the expression levels of SGLT1 were significantly correlated with those of EGFR. Pearson product-moment correlation coefficient of SGLT1 and EGFR was 0.89 (P = 0.016). The immunohistochemical study using the surgical specimens in 52 patients with tongue SCC also showed a significant correlation between SGLT1 and EGFR. Moreover, SGLT1/EGFR expression was inversely related to tumor differentiation among the 5 clinicopathological factors (P = 0.004). SGLT1/EGFR coexpression might be required in the de-differentiation of OSCC, but further study is needed to clarify the implication of these proteins in the manifestation of malignancy and clinical significance.