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It is well known that lymph node metastasis is a major prognostic factor in patients with oral squamous cell carcinoma (OSCC). 30-40% of patients with OSCC have already undergone regional metastasis at diagnosis. The survival rate of patients with metastasis is reduced by more than 50%. Therefore, prevention and early detection of metastasis are very important to increase the survival rate of patients. Many investigators have studied the molecular mechanism of metastasis and tried to develop the molecules to inhibit any step of metastatic cascade. Among those molecules, an interest in the metastasis suppressor gene has been increasing. Expression of metastasis suppressor KiSS-1 has shown to be significantly related to poor clinical outcome and worse survival rate of patient in various malignancies of different organs. In addition, our previous study in OSCC also revealed that downregulation of KiSS-1 expression correlated with the presence of cervical lymph node metastasis, one part of tumor progression. Therefore, further investigation was needed to identify the molecular function of KiSS-1 using OSCC cell line and to evaluate the possibility of KiSS-1 as a new therapeutic target.