Phloroglucinol is a polyphenol compound with free radical scavenging, anti-inflammatory and antitumor activity. In this study, we investigated the anticancer effects of phloroglucinol on insulin-like growth factor-1 receptor (IGF-1R) signaling in HT-29 human colon cancer cells. Apoptosis was evaluated using 4',6-diamidino-2-phenylindole (DAPI) staining, which clearly demonstrated cell shrinkage and condensed nuclei. Treatment with a pan-caspase inhibitor reduced the expression of phosphatidylinositol-3-kinase (PI3K)/Akt, which could induce apoptosis through IGF-1R signaling pathways. Treatment with phloroglucinol significantly inhibited the expression of Ras, Raf, mitogen-activated protein kinase (MEK), extracellular-signal regulated kinase (ERK) phosphorylation, PI3K and Akt. Phloroglucinol also decreased mammalian target of rapamycin (mTOR) and expression of its downstream effectors p70S6 kinase and translation initiation factors elF4B and RPS6. These results demonstrate that IGF-1R activates PI3K/Akt/mTOR and Ras/ERK-MAPK downstream signaling pathways, which has important implications for understanding the roles of cell growth pathways in colon cancer cell tumorigenesis.