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Background::Colon cancer is responsible for increasing the death rate worldwide. Commonly used anticancer drugs have various side effects and their clinical usage must be restricted due to their toxicity.Objective::The present research aimed to evaluate the anticancer potential of Lepidium sativum L. (LS) seeds aqueous extract against azoxymethane/dextran sodium sulfate (AOM/DSS) inducedcolon cancer in male albino mice.Methods::Low (200 mg/kg) and high (400 mg/kg) doses of LS seeds extract were used to treat induced colon cancer in different stages.Results::The present results report that LS treatment for mice with colon cancer especially in high dose, decreases colon polyps/tumor incidence and size, tissues disorder, expression of P53 and increases apoptosis in colon tissue. Moreover, LS decreases micronucleus induction in polychromatic (PCE), increases PCE/normochromatic erythrocytes ratio and decreases the percentage of sperm abnormalities.Conclusion::The present study reports anticancer potential of LS for induced colorectal cancer mice by ameliorating the inflammatory steps of colon.