OBJECTIVE: To study the expression of signal transducer and activator of transcription 3 (Stat3), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in Wilms' tumor and their roles in the development of Wilms' tumor. METHODS: The expression of Stat3, HIF-1α and VEGF were detected by the immunohistochemical staining in 52 specimens from Wilms' tumor tissues, 47 from adjacent kidney tissues and 8 from normal kidney tissues. The expression intensity was analyzed by computer image processing. RESULTS:The expression of Stat3, HIF-1 and VEGF were significantly up-regulated in Wilms' tumor tissues compared to those in adjacent tissues and normal kidney tissues (P< 0.05). Stat3 and VEGF proteins in Wilms' tumor tissues of stage III-IV and high risk histopathology were significantly higher than those of stage I-II and low risk histopathology. The higher expression of HIF-1 in Wilms' tumor tissues was shown in tumors with high risk histopathology and tumor size ≥ 6 cm. CONCLUSIONS: Increased expression of Stat3, HIF-1 and VEGF were found in Wilms' tumor tissues, and may be related to the development and angiogenesis of Wilms' tumor. Stat3 may regulate the expression of HIF-1 and VEGF, so it could be an effective target for inhibiting VEGF expression and angiogenesis of Wilms' tumor.