Δ12-Prostaglandin J2 (Δ12-PGJ2) is one of cyclopentenone prostaglandins. The Δ 12-PGJ2 is known to induce apoptosis of tumor cells, however, it's action mechanism is not clear. It has recently been reported that STAT3 is involved in tumorigenesis. In the present study, we investigated the role of STAT3-interacting protein (STIP1) in the cytotoxicity of Δ 12-PGJ2, since STIP1 was recently reported as a modulator of STAT3 activation by specifically binding to inactive (unphosphorylated) STAT3. The effect of Δ12-PGJ2 was observed in stably overexpressing Neuro-2A cells transfected with full cDNA of STIP1, and cytotoxicity of Δ 12-PGJ2 in the transfected cells was increased, compared with the vector control cells. The cytotoxicity of Δ12-PGJ2 treatment was significantly accentuated by pretreatment of the STIP1-transfected cells with protein kinase inhibitor, genistein, and less activation of STAT3 in STIP1-transfected cells was shown, compared with the vector control cells. Expression of bax was also increased in the STIP1-transfected cells. These data suggest that STIP1 inhibits cell growth via inhibition of STAT3 activation in Δ12-PGJ2 treatment.