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Objectives Patchouli alcohol is one of the abundant compounds isolated from essential oil of Pogostemon cablin and shows anti-inflammatory, anti-obese and anti-cancer activities. The current study was designed to investigate if treatment of patchouli alcohol exhibits tumor suppressive activity in colon cancer mouse model and define a reliable mechanism using in vitro culture system using colon cancer cell lines. Methods Twenty seven 4-week old Apc min/+ mice were assigned into one of three groups (n = 9) and patchouli alcohol (0, 25 or 50 mg/kg body weight) was orally administered three times a week for six weeks before/after treatment of dextran sulfate sodium (DSS). At age 10-week old, all animals were sacrificed, colon and small intestines were collected, and the number and size of tumors were counted and measured. Human colon cancer cell lines (HT-29, Lovo and Caco-2) were treated with different concentration of patchouli alcohol for 48 hours. And cell cycle distribution was measured using FACS and luciferase reporter gene assay was performed to elucidate reliable mechanism of anti-cancer activity. Results In vivo study indicated that the number of tumor and tumor load was significantly decreased in a dose-dependent manner by administering patchouli alcohol (25 and 50 mg/kg body weight). Treatment of 100 µM patchouli alcohol led to G1 arrest with decreased cell proliferation. Reporter gene assay showed decreased transcriptional activity of β-catenin in patchouli alcohol-treated cells. Conclusions Patchouli alcohol prevents formation of adenoma polyps by repressing cancer cell growth/division via downregulating transcriptional activity of β-catenin in colon cancer model. Funding Sources NIFA Hatch grant. Supporting Tables Images and/or Graphs