The functions of mouse liver NK1.1 + T (NKT) cells stimulated with α-galactosylceramide (α-GalCer) are enhanced age dependently, and the antitumor and anti-metastatic effect in the liver is dependent on IFN-γ. However, hepatic injury is independent of IFN-γ and Fas/Fas-ligand dependent. The aim of this study is to investigate how tumor necrosis factor is involved in the α-GalCer-mediated immune phenomena.C57BL/6 mice were intraperitoneally treated with anti-TNF antibody 1h before α-GalCer injection, and Fas-ligand expression of NKT cells, the serum ALT levels and histopathological findings of the liver, kidney and lung and mortality after α-GalCer injection were evaluated. IFN-γ production and antitumor immunity in the liver after the intravenous injection of EL-4 cells were also assessed.Serum TNF levels after α-GalCer injection increased age dependently in mice. Anti-TNF Ab reduced Fas-ligand (Fas-L) expression of NKT cells while it completely inhibited organ injuries induced by α-GalCer and thereby reduced the mortality of old mice, whereas it did not affect the IFN-γ production from NKT cells, the antitumor immunity in the liver nor the mouse survival after EL-4 injection.NKT cells activated by α-galactosylceramide participated in either antitumor immunity or hepatic injury using IFN-γ and TNF/Fas-L, respectively.