The comparative effect of raw red chili and red chili treated by gamma irradiation or microwave pasteurization with or without 5-fluorouracil on experimentally induced colon cancer in rats was investigated. Dimethylhydrazine was used to induce colon cancer which is histologically similar to and comparable with human neoplasm. Histopathological examination of dimethylhydrazine-treated rats demonstrated epithelial and goblet cell hyperplasia as well as preneoplastic changes of the rat colon expressed by loss of polarity of the nuclei and abnormal mitosis. The preneoplastic changes were developed to adenocarcinoma in 80% of cases. The liver showed different pathological pictures that included dysplastic changes, preneoplastic foci, and oval cell proliferation. We observed that red chili with or without 5-fluorouracil inhibited colon adenocarcinoma. The gamma red chili either alone or with 5-fluorouracil was the best groups. The gamma irradiated red chili alone decreased epithelial and goblet cell hyperplasia and preneoplastic changes in colon and dysplastic changes, oval cell proliferation, and Kupffer cell hyperplasia in the liver. The gamma irradiated red chili with 5-fluorouracil inhibited the preneoplastic changes in colon. It was concluded that the sanitization of red chili by gamma irradiation either alone or with 5-fluorouracil was more beneficial from the human health point of view than that by microwave.The comparative effect of raw red chili and red chili treated by gamma irradiation or microwave pasteurization with or without 5-fluorouracil on experimentally induced colon cancer in rats was investigated. Dimethylhydrazine was used to induce colon cancer which is histologically similar to and comparable with human neoplasm. Histopathological examination of dimethylhydrazine-treated rats demonstrated epithelial and goblet cell hyperplasia as well as preneoplastic changes of the rat colon expressed by loss of polarity of the nuclei and abnormal mitosis. The preneoplastic changes were developed to adenocarcinoma in 80% of cases. The liver showed different pathological pictures that included dysplastic changes, preneoplastic foci, and oval cell proliferation. We observed that red chili with or without 5-fluorouracil inhibited colon adenocarcinoma. The gamma red chili either alone or with 5-fluorouracil was the best groups. The gamma irradiated red chili alone decreased epithelial and goblet cell hyperplasia and preneoplastic changes in colon and dysplastic changes, oval cell proliferation, and Kupffer cell hyperplasia in the liver. The gamma irradiated red chili with 5-fluorouracil inhibited the preneoplastic changes in colon. It was concluded that the sanitization of red chili by gamma irradiation either alone or with 5-fluorouracil was more beneficial from the human health point of view than that by microwave.