BACKGROUND: Hypoxia seems to be an influencing factor for oral squamous cell carcinomas (SCC), and several immunohistochemical markers have been discussed in this regard. The aim of the present study was to evaluate preoperative hemoglobin levels as a prognostic factor for oral SCC. MATERIALS AND METHODS: The files of 287 patients who had been treated for oral SCC between 1999 and 2008 were studied retrospectively. Hemoglobin levels between 1 and 5 days prior to surgical treatment were compared to Tumor (T)- and Nodal (N)- status, local recurrence, and lymph node metastases rate. The minimum follow-up period was 12 months. RESULTS: From a total of 287 patients with oral SCC, 205 (71.4%) were in the normal hemoglobin (Hb) group (female Hb ≥ 12.0 g/dl; male Hb ≥ 13.0 g/dl), 53 (18.5%) in the mild anemia (female Hb = 11.0-11.9 g/dl; male Hb = 11.0-12.9 g/dl), and 29 (10.1%) in the severe anemia group (female & male Hb<11.0 g/dl). Anemia was significant for the development of lymph node metastasis (p = 0.005) as well as for local recurrence (p = 0.001). No significant correlation was found to the initial T status (p = 0.183). CONCLUSION: Our data suggests that an Hb of below 11 g/dl contributes to and is an indicator for a poor prognosis. Consequently, pre-treatment Hb corrections may significantly improve outcome, but further investigations, including blood transfusion/application of erythropoietin due to tumor anemia, independent of intraoperative blood-loss are necessary to ascertain their role in an improved survival.