Objective: To establish an animal model of pulmonary metastasis from nasopharyngeal carcinoma (NPC) and to investigate differential genes associated with pulmonary metastasis. Methods: CNE cell line was used to construct the stable metastasis CNE/Luc cell line which steadily expresses the fluorescent enzyme genes. The CNE/Luc cells were injected into immunodeficiency mice through tail vein, and with the in vivo imaging technology, the mice with pulmonary metastasis were filtered out. The pulmonary metastasis cells, were separated and injected into the tail vein of other nude mice to obtain the tissue-specificity metastasis cells confirmed by fluorescent imaging system. Based on the gene chip, the differential genes associated with pulmonary metastasis for NPC were found. Results: The gene expression profiles of nasopharyngeal carcinoma cell line CNE/Luc and their lung metastasis-associated subpopulation CNE/Luc-2 were constructed by gene chip technology. Ten metastasis-related genes were screened by software analysis, namely as TP53, PIK3CA, MET, KRAS, VEGFA, EDNRB, GSK3B, FOXO3, SOD2, and BIRC3. Conclusions: Some genes including TP53, PIK3CA, MET, KRAS, VEGFA, EDNRB, GSK3B, FOXO3, SOD2, and BIRC3 are indicated to have important roles in the lung metastasis of nasopharyngeal carcinoma.