In order to investigate the expression of nerve growth factor (NGF) and hypoxia inducible factor-1 alpha (HIF-1 alpha) and its correlation with angiogenesis in non-small cell lung cancer (NSCLC), paraffin-embedded tissue blocks from 20 patients with NSCLC were examined. Twenty corresponding para-cancerous lung tissue specimens were obtained to serve as a control. The expression of NGF, HIF-1 alpha, and vascular endothelial growth factor (VEGF) in the NSCLC tissues was detected by using immunohistochemistry. The microvascular density (MVD) was determined by CD31 staining. The results showed that the expression levels of NGF, HIF-1 alpha and VEGF in the NSCLC tissues were remarkably higher than those in the para-cancerous lung tissues (P < 0.05). There was significant difference in the MVD between the NSCLC tissues (9.19 +/- 1.43) and para-cancerous lung tissues (2.23 +/- 1.19) (P < 0.05). There were positive correlations between NGF and VEGF, between HIF-1 alpha and VEGF, and between NGF and HIF-1 alpha in NSCLC tissues, with the spearman correlation coefficient being 0.588, 0.519 and 0.588, respectively. In NSCLC tissues, the MVD had a positive correlation with the three factors (P < 0.05). Theses results suggest that NGF and HIF-1 alpha are synergically involved in the angiogenesis of NSCLC.