Background: As conventional pH-controlled colon-targeted system used for oral drug delivery often shows a poor performance, a more effective way to preserve poorly water-soluble drug from releasing in upper gastrointestinal tract should be researched. Method: The objective of this study was to develop a novel colon-targeted drug delivery system using guar gum and Eudragit as enzyme-and pH-based materials. Lansoprazole, a poorly water-soluble drug was used as model drug. Under three different conditions, the in vitro drug release behaviors of this newly developed system was evaluated, using beta-mannanase, rat cecal content, and human fecal media to simulate the pH and enzyme during intestinal transit to the colon. Results: The released amount of lansoprazole in simulated small intestine fluid (pH 6.8) after 5 hours was less than 10% from the pH- and enzyme-controlled tablets compared with 80.01 +/- 0.3% in rat cecal content medium (pH 7.4). The degradation ability of human fecal slurries on PECCT-PT was independent of human age and gender. beta-Mannanase did not have a similar effect on the degradation of polysaccharide as rat cecal enzymes and human fecal enzymes in our study. Scanning electron microscope study indicated that the dissolution mechanism of PECCT-PT should be corrosion. Conclusion: The above results indicated this system could be served as a potential carrier to deliver poorly water-soluble drug specifically to the colon.