Objective To observe the regional expression of hypoxia inducible factor-1alpha; (HIF-1alpha;) in retinoblastoma and its relationships with vascular endothelial growth factor (VEGF), Bax and Ki-67. Methods Immunohistochemical study for HIF-1alpha;, VEGF, Bax and Ki-67 was performed in 39 paraffinaceous examples of retinoblastoma. Each pathological section was divided into five regions: the surface region, the central part, the bottom part, the choroidal region and seeding tumors. The expressions, correlations and distributional differences of these factors were all invested both integrally and regionally. Results In the 39 cases of retinoblastoma, 10 cases (25.6%) were negative for HIF-1alpha;; 29 cases (74.4%) were positive for HIF-1alpha;, including 17 cases (43.6%) (+), 12 cases (30.8%) (++). Regionally, HIF-1alpha; was positive in 71.1%, 36.8%, 84.2%, 54.5% and 82.1% of the cases in the surface region, the central part, the bottom part, the choroidal region and seeding tumors, respectively, which was statistically reliable (chi;2=24.55，P＜0.001). The positive rate of VEGF, Bax and Ki-67 was 53.8%, 66.7% and 59.0%, respectively. In different regions, the positive rates of VEGF and Bax were different (chi;2=26.77, 22.79; P＜0.001), but there was no regional distinctions in the expression of Ki-67 (chi;2=0.47, P=0.976). Both the expression of VEGF and Bax had a positive correlation with that of HIF-1alpha;(rs=0.48, 0.39; P=0.002, 0.021), but there was no relationship between the expressions of Ki-67 and that of HIF-1alpha; (rs=0.09, P=0.606). Regionally, the expressions of VEGF, Bax and HIF-1alpha; shared similar distributional features: positive rates were higher in the surface region, bottom part and seeding tumors, and were lower in the central part and choroidal region, which was different from the expression of Ki-67. Conclusion The anoxic zones are more likely to be located in the marginal parts in retinoblastoma, and the expressions of VEGF and Bax had a positive correlation with that of HIF-1alpha; in different regions in retinoblastoma.