The primary reasons for the treatment failure of patients with oral tongue squamous cell carcinoma (OTSCC) are metastasis and tumor recurrence. Identifying the exact mechanisms underlying metastasis is a key point in improving patient prognosis. It has been reported that a hypoxic microenvironment plays an important role during the metastasis of malignancies. We found that the expression of fibronectin type III domain containing 3B (FNDC3B) is positively correlated with lymph node metastasis and advanced cTNM stage of OTSCC by IHC assay and correlation analysis. Furthermore, we found that knockdown of FNDC3B could suppress the migratory and invasive abilities of OTSCC cells. In addition, treating OTSCC cells with CoCl2 (a hypoxia mimetic agent) upregulated the mRNA and protein expression of FNDC3B via HIF-1 alpha. Moreover, the resultant increase in FNDC3B expression significantly induced epithelial-mesenchymal transition (EMT) in OTSCC cells. The present study elucidated the important role played by FNDC3B in OTSCC metastasis and indicates FNDC3B as a potential target for the treatment of OTSCC metastasis. However, many questions remain to be explored.