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AIM: To study the expression of hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF)in hepatocellular carcinoma (HCC) and the impact on neovascularization and survival.METHODS: Expressions of HIF-1α, VEGF and microvessel density (MVD) are studied through immunohistochemistry in 36 cases of HCC and the corresponding paraneoplastic tissue and 6 cases of normal liver tissue. The relationship of the expressions of HIF-1α and VEGF with the clinicopathological data and survival are analyzed.RESULTS: The positive rate of VEGF in HCC was 32/36,which is significantly higher than that in paraneoplastic tissue and normal liver tissue (P＜0.05). The expression of HIF-1α in HCC tissue is 24/36, also higher than that in paraneoplastic tissue and normal liver tissue (P＜0.05). The expression of VEGF and HIF-1α in HCC with microscopic venous invasion is significantly higher than that in HCC without microscopic venous invasion (P＜0.05). Spearman correlation analysis does not only show the expression of HIF-1α as correlated with the expression of VEGF (rs = 0.459, P＜0.01), but it also shows the expression of HIF-1α and VEGF as correlated with MVD (rs = 0.412 and 0.336, respectively, P＜0.05). The differences of the survival rates among VEGF positive group and VEGF negative group are significant (P＜0.05), whereas the differences of the survival rates among the HIF-1α negative group and positive group are not significant (P＞0.05).CONCLUSION: HIF-1α plays important roles in neovascularization in HCC possibly through regulation of VEGF transcription.