Vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor receptor 3 (VEGFR-3) play important roles in lymphangiogenesis of malignant tumors; their expression are closely related to lymphatic metastasis of malignant tumors. This study was designed to investigate the expression and clinical significance of VEGF-C and VEGFR-3 in non-small cell lung cancer (NSCLC).The expression of VEGF-C and VEGFR-3 in 77 specimens of NSCLC were detected by immunohistochemistry; their correlations to lymphatic vessel density (LVD), tumor size, histological type, differentiation, lymphatic metastasis, clinical recurrence, and survival time of the patients were analyzed.Positive rate of VEGF-C was 58% in NSCLC, and that of VEGFR-3 was 42%. The expression of VEGF-C protein was negatively correlated with the differentiation of NSCLC (r=-0.32, P=0.018). The expression of VEGF-C and VEGFR-3 were related to lymphatic metastasis, LVD, tumor size, and survival time of the patients. The expression of VEGF-C was positively related with that of VEGFR-3 (r=0.23, P=0.045).The expression of VEGF-C and VEGFR-3 are closely related with lymphatic metastasis and prognosis of NSCLC; their high expression indicate high risk of lymphatic metastasis and poor prognosis.