In patients with HNC anemia is common symptom and usually consist of both components: treatment related anemia and anemia of chronic disease. The disparity between production and elimination of erythrocytes is a direct reason of anemia which is characterized by low levels of circulating red blood cells and hemoglobin (Hb), reduced number of reticulocytes (Ret), inadequate secretion of erythropoietin (Epo) and disturbances in iron metabolism. Although the thorough mechanisms of anemia of chronic disease is not fully understood, it causes tissue hypoxia that increases resistance to radiotherapy. The aim of this study was to assess the clinical utility parameters of the erythrocytic system: reticulocytes (Ret), immature reticulocyte fraction (IRF), the concentration of Epo and sEpoR as a marker of tumor hypoxia. Between 01/2009 and 08/2013 186 patients with squamous cell cancer of oral cavity (5%), nasopharynx (7%), oropharynx (30%), hypopharynx (10%) and larynx (48%) were treated with radiotherapy alone (40%) or combined with chemotherapy (60%). There were 19%, 33%, 27%, and 21% patients with T1, T2, T3 and T4 tumor stage and 48%, 11%, 29%, and 11% patients with N0, N1, N2 and N3 nodal stage of disease respectively. Epo, sEpoR and parameters of the red blood cell system were estimated in plasma or blood before and immediately after treatment completion. Strong negative correlation before treatment has been found in patients with anemia (Hb< 11 g/ml) between Hb levels and Epo (p=.0004), Ret (p=.04) and IFR (p=.0001). Additionally, a negative correlation in patients with anemia has been found between Hb levels and Epo (p=.005) and IRF (p=.0001) after treatment. Significantly longer overall survival (OS) has been found for patients with decreased Epo levels (p=.01) and elevated Hb levels (p=.03) before treatment and elevated IFR (p=.04) after treatment. Also, in the multivariate analysis, pre- and posttreatment Epo levels were an independent prognostic factors for shorter OS (p=.02; p= .004; respectively). In patients with HNC, anemia is a chronic disease which may stimulate erythropoiesis. IFR may indicate increased and ineffective erythropoiesis which correlates with increased risk of death. Pre- and posttreatment Epo are prognostic determinants of OS in this group of patients.