We examined effects of recombinant p53-expressing adenovirus combined with thermoradiotherapy in 8 head and neck squamous cell carcinoma (SCC) cell lines to improve the outcomes of the threatment of advanced head and neck cancer. The p53 gene therapy did not improve the discrepancy between thermoradiosensitivities among the 8 SCC cell lines. However, p53 gene therapy improved the effects of thermoradiotherapy in all 8 cell lines, and there were significant differences in four situations of the HSC4 44degreesC (p=0.032), SAS at 44degreesC (p=0.029), the KB at 43degreesC (p=0.025), and the Ca9-22 43degreesC (p=0.020). In comparing the survival rates of thermoradiotherapy with those of thermotherapy and radiotherapy, thermoradiotherapy demonstrated actual survival rates less than theoretical survival rates based on the survival rates of thermotherapy multiplied by the survival rates of radiotherapy in almost all treatments of thermoradio-gene therapy of the 8 SCC cell lines. These results demonstrate that thermoradiotherapy combined with p53 gene therapy may be a useful tool in treating SCC cells.