The effect of hypoxia inducible factor-1alpha (HIF-1alpha) on vascular endothelial growth factor C (VEGF-C) and the correlation between HIF-1alpha and lymphangiogenesis and lymph nodes metastases (LNM) in pancreatic cancer were investigated. Immunohistochemical SP method was used to detect the protein expression of HIF-1alpha and VEGF-C, and Lymphatic vessel density (LVD) was determined by stain of VEGFR-3, collagen type IV in 75 pancreatic head cancers from regional pancreatectomy (RP) during Dec. 2001 to Dec. 2003. The relationship between HIF-1alpha and VEGF-C, lymphangiogenesis, LNM was analyzed statistically. The results showed that the positive expressionrate of HIF-1alpha and VEGF-C in pancreatic cancer tissues was 48.00 % (36/75) and 65.33 % (49/75) respectively. In positive group of HIF-1alpha, the positive rate of VEGF-C and LVD, and LVD rate was 80.56 % (29/36), 13.22+/-3.76 and 88.89 % (32/36) respectively, and in negative group of HIF-1alpha, positive rate of VEGF-C and LVD was 51.28 % (20/39), 5.98+/-2.17 and 66.67 % (26/39) respectively (P<0.01 or P<0.05). It was suggested that HIF-1alpha could promote the expression of VEGF-C, lymphangiogenesis and LNM in pancreatic cancer.