In this study, nicotine-induced upregulation of CHRNA5 was found to promote the metastatic potential of LSCC cells in vitro and in vivo, and CHRNA5 was found to be significantly associated with lymph node metastasis and poor prognosis in patients with LSCC. This evidence concerns the gene CHRNA5 and metastatic malignant neoplasm in the lymph nodes.