Technical Abstract: Noni (Morinda citrifolia) has been extensively used in folk medicine by Polynesians for over 2000 years and recent studies have shown that noni has a wide spectrum of therapeutic activities including inhibition of angiogenesis, anti-inflammatory effects, and anti-cancer activities. We recently reported that intraperitoneal (i.p.) injection of fermented noni exudates (fNE) induced significant tumor rejection in a S180 mouse sarcoma tumor model and demonstrated that natural killer (NK) cells are the major players in fNE induced anti-tumor activity. In this report, we partitioned fNE into three fractions and examined their antitumor effects by i.p. injection or as a water supplement. The in vivo animal study results show that the n-butanol fraction of fNE (BuOH), when delivered by i.p. injection, effectively rejected (100%) tumor challenge and eradicated existing tumors (75%). When delivered as a water supplement, 62.5% of the mice receiving the n-butanol or ethyl acetate fractions rejected tumor cells. The tumor resistant mice effectively rejected further and higher doses of tumor challenge, indicating that the immune system was activated. The findings not only confirm our early report that fNE has antitumor activity but also demonstrated that the n-butanol fraction of fNE contains the active antitumor components, which will be further identified. More importantly, the antitumor effect of fNE and its fractions as water supplements renders a significant potential for identifying novel and powerful new dietary products for cancer prevention.