Aim The aim of this work was to identify the role of the NADPH oxidase Nox4 for tumour angiogenesis in a slow growing tumour model in mice. Methods Tumour angiogenesis was studied in tumours induced by the carcinogen 3‐methylcholanthrene (MCA) in wild‐type and Nox knock out mice. Mice were sacrificed when the tumour reached a diameter of 1.5 cm and tumour tissue was used for histological and molecular analysis. Results 3‐methylcholanthrene induced fibro sarcoma in wildtype, Nox1y/‐, Nox2y/‐ and Nox4‐/‐ mice. Histological analysis of vessel density using anti‐CD31 staining showed a significant 38% reduction in tumour vascularization in fibro sarcomas of Nox4‐/‐ mice. In contrast tumour angiogenesis was doubled in Nox1 knock out mice, whereas knock out of Nox2 had no effect on tumour vessel density. As underlying mechanisms we identified a defect in hypoxia signalling in Nox4‐/‐ mice. Hypoxia‐ inducible factor 1‐alpha (Hif‐1α) accumulation in the tumours was attenuated as was the expression of the Hif‐1α‐dependent pro‐angiogenic genes vascular endothelial growth factor‐A, glucose transporter 1 and adrenomedullin. Conclusion By regulating the tumour vessel density through stabilization of Hif‐1α and induction of VEGF expression Nox4 promotes tumour angiogenesis and may represent a novel target for anti‐angiogenic tumour therapy. This article is protected by copyright. All rights reserved.