Endogenous tumor necrosis factor (enTNF) acts as a cross-resistant factor against the cytotoxicity caused by exogenous TNF, doxorubicin, and heat, not only via induction of manganous superoxide dismutase, but also via enhancement of the heat shock element binding activity of heat shock factor 1, followed by augmentation of HSP 72 expression. These findings suggest that prediction of the efficacy of various therapeutic modalities against cancer is possible by measurement of enTNF expression.