In our study, we investigated the expression level of SEC62 and SOX2 in tissue specimens of HNSCC and CUP patients and examined their effect on the migration and proliferation of HNSCC cells in vitro as well as the patients’ survival data to determine their role in the process of lymphatic metastasis in HNSCC patients and their contribution to CUP biology. The gene discussed is SOX2; the disease is head and neck squamous cell carcinoma.