Proliferator-activated receptor&ggr;(PPAR&ggr;) is a nuclear receptor, which mainly associates with adipogenesis, but also appears to facilitate cell differentiation or apoptosis in certain malignant cells. This apoptosis induction by PPAR&ggr;is increased by co-stimulation with tumor necrosis factor (TNF)-&agr;-related apoptosis-inducing ligand (TRAIL), a member of the TNF family. In this study, we investigated the effect of PPAR&ggr;on Fas-mediated apoptosis in hepatocellular carcinoma (HCC) cell lines. PPAR&ggr;was expressed on all seven HCC cell lines and located in their nuclei. 15-Deoxy-&Dgr;-12,14-prostaglandin J2(15d- PGJ2), a PPAR&ggr;ligand, inhibited cellular proliferation in HepG2, SK-Hep1 or HLE cells, unlike pioglitazone, another PPAR&ggr;ligand, which did not have a significant influence on proliferation of these cells. However, 15d-PGJ2facilitated Fas-mediated HCC apoptosis that could not be induced by Fas alone. These results suggest that PPAR&ggr;can augment TNF-family-induced apoptosis.