Technical Abstract: Phytochemicals are a rich source of chemoprevention agents but their effects on modulating the Wnt/ß-catenin signaling pathway have remained largely uninvestigated. Aberrantly activated Wnt signaling can result in the abnormal stabilization of ß-catenin, a key causative step in a broad spectrum of cancers. Here we report the modulation of lithium chloride-activated canonical Wnt/ ß-catenin signaling by phytochemicals that have antioxidant, anti-inflammatory or chemopreventive properties. The compounds were first screened with a cervical cancer-derived stable Wnt signaling reporter HeLa cell line. Positive hits were subsequently evaluated for ß-catenin degradation, suppression of ß-catenin nuclear localization and down-regulation of downstream oncogenic targets of the Wnt/ß-catenin pathway. Our study shows novel degradation of the ß-catenin protein in HeLa cells by avenanthramide 2p (a polyphenol) and triptolide (a diterpene triepoxide) from oats and a Chinese medicinal plant respectively. The findings present avenanthramide 2p as a potential chemopreventive dietary compound that merits further study using in vivo models of cancers; they also provide a new perspective on the molecular mechanisms of Triptolide biological activity. The findings present avenanthramide 2p as a potential chemopreventive dietary compound that merits further study using in vivo models of cancers; they also provide a new perspective on the molecular mechanisms of triptolide biological activity.