Tumor necrosis factor(TNF) has known to have synergistic cytotoxic effect when used with anticancer chemotherapeutic agents. We studied the synergistic cytotoxic effect of TNF and anticancer chemotherapeutic agents (doxorubicin hydrochloride, cisplatin, 5-fluorouracil, Methotrexate) on squamous cell carcinoma celliness(SNU-46, SNU-899, SNU-1041) cultured from head and neck cancer. The results were as follows : 1) Cisplatin in combination with TNF increased cytotoxicity of SNU-46 cell line by 79.18%, of SNU-899 cell line by 55.40%, and of SNU-1041 cell line by 26.46% than cisplatin alone(p<0.001 in each cell line). 2) 5-fluorouracil in combination with TNF increased cytotoxicity of SNU-46 cell line by 12.89%(p<0.001), of SNU-899 cell line by 6.16%(p>0.01), and of SNU-1041 cell line by 0.87%(p>0.01) than 5-fluorouracil alone. 3) Doxorubicin hydrochloride in combination with TNF increased cytotoxicity of SNU-899 cell line by 11.33%(p<0.01), and of SNU-46 cell line by 1.13%(p>0.01), but increased cell viability of SNU-1041 cell line by 1.9%(p>0.01) than doxorubicin hydrochloride alone. 4) Methotrexate in combination with TNF increased cell viability of SNU-46 cell line by 0.58%(p>0.01), and of SNU-1041 cell line by 2.68%(p>0.01) than methotrexate alone, but showed same cell viability of SNU-899 as methotrexate alone. Cisplatin and 5-fluorouracil in combination with TNF showed synergistic better cytotoxicity than anticancer chemotherapeutic agent alone. Although TNF is not used in anticancer chemotherapy in human yet, it can give synergistic effect to cisplatin and 5-fluorouracil in combination anticancer chemotherapy.