Colon cancer is one of the most common cancers in many regions of the world and is prevented by dietary interventions. This study aimed to examine the chemopreventive effect of silk protein, sericin, against 1,2-dimethylhydrazineinduced colon tumorigenesis in rats in comparison with control casein diet. The result showed that 5 out of 14 of casein fed rats developed colon tumors, whereas only 1 from 14 sericin fed rats exhibited tumors. Consumption of sericin prior to or during carcinogen exposure reduced the number of aberrant crypt foci. In addition to crypt number, crypt multiplicity was less progressive in sericin fed group. The sericin diet also exhibited anti-oxidant activity as evidenced by reduced lipid peroxidation in the colons. This finding suggests that consumption of sericin may reduce the progression of colon tumor development possibly by suppressing the initiation and promotion stages of colon tumorigenesis.