Recent epidemiology and laboratory studies indicate that regular taking of aspirin and other non-steroidal anti-inflammatory drugs(NSAIDs) may reduce the risk of colorectal, esophageal, stomach and pancreatic cancers and other digestive cancers. Thus, aspirin and other NSAIDs may be an effective chemoprevention agent for digestive cancers. On the other hand, this protection effort may be beneficial to the course of the intervention, regression and prevention of cancer lesions. The possible mechanism of NSAIDs chemoprevention may be: (1) reducing the synthesis of prostaglandin(PG) and inhibiting cyclo-oxygenase(COX) activity; (2) inducing apoptosis in epithelial cells of the gastro-intestinal origin; (3) obstructing signaling transduction pathways of COX and PG. Now, chemoprevention of NSAIDs has become focus of research on cancer secondary prevention, as its protective effects of chemoprevention of digestive cancer have been determined. NSAIDs, especially selective COX-2 inhibitor may be a novel useful chemoprevention agents for digestive cancer and their precursor lesions in future.