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Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in the serum of 34 patients with head and neck cancer (HNC) undergoing locoregional radiotherapy (RT) were examined. The aim of the RT was definitive in 19 and postoperative adjuvant in 15 patients. Serum TNF-α and IL-6 levels were recorded before RT and after the completion of the fifth week of RT. The mean TNF-α levels before and after RT were 28.26 ± 2.87 and 83.03 ± 7.47, and the mean IL-6 levels were 61.56 ± 14.32 and 122.45 ± 30.66, respectively. The statistical analysis yielded a significant rise in TNF-α levels with RT in all patients (p < 0.0001) and also in IL-6 levels in patients treated with postoperative adjuvant RT (p = 0.001). Irradiation is likely to cause an acute phase response, and the cytokines studied may be used to monitor this clinically important response in further trials.