Head and neck squamous cell carcinoma has still a poor prognosis. Since angiogenesis is crucial for tumor growth, a better understanding of the potential clinical relevance as well as the interactions between the numerous proangiogenic growth factors is essential to develop improved therapeutic strategies in these tumors. Expression levels of eight growth factors known to induce angiogenesis (HGF, bFGF, VEGF‐A, VEGF‐D, PDGF‐AB, PDGF‐BB, G‐CSF, and GM‐CSF) were quantitatively measured by ELISA in homogenates of 41 head and neck squamous cell carcinomas. In addition, microvessel density and protein localization of growth factors were assessed by immunohistochemistry. Statistical analysis was performed to assess interrelationships between growth factors analyzed and to correlate protein levels with patient outcome. In 90% of the tissues at least 4/8 growth factors analyzed were detectable. Highest amounts and most frequent expression were found for HGF, bFGF and VEGF‐A while PDGF‐AB and PDGF‐BB were present in two‐thirds and G‐CSF and GM‐CSF in approximately half of the cases. Although there was no significant relation to microvessel density, we identified significant associations for bFGF with HGF and G‐CSF as well as of PDGF‐AB with those of VEGF‐A and PDGF‐BB. For the first time we demonstrate that expression levels of HGF as well as that of bFGF and G‐CSF in head and neck squamous tumors are negative prognostic factors for patient survival. Our data indicate a network of interrelated and prognostically relevant growth factors in these tumors that have to be taken into consideration when planning an antiangiogenic and antitumor therapy. (Cancer Sci 2009; 100: 1210–1218)