METHODS Curcumin is a polyphenol with a variety of pharmacologic effects. We evaluate the effect of dietary curcumin on the severity of repeated colitis-associated colorectal cancer. RESULTS Six-week-old C57BL/6 mice were randomized into two dietary groups: standard diet and curcumin at 0.6% diet. The mice were exposed to 15 cycles of 0.7% dextran sodium sulphate for 1 week followed by distilled water for 10 days. After curcumin diet, the disease activity index presented a statistical reduction in the last cycles, macroscopic tumors were not seen and the microscopic study showed minor neoplasic lesions with respect to standard diet-group. β-Catenin translocation to the cytoplasm and/or nucleus was observed in the tumor tissue, but this translocation and its intensity were significantly minor in the curcumin diet-DSS animals. Cytokines as tumor necrosis factor-α and IFN-γ were significantly diminished in DSS-animals fed with curcumin. Conversely, non-modification of p53 expression was observed and cyclo-oxygenase-2 and inducible nitric oxide synthase were significantly reduced in the curcumin diet-DSS group. CONCLUSIONS We demonstrate the protective/preventive effect of curcumin in the progression of colorectal cancer associated to colitis, which was correlated with a lowered immunoreactivity of ß-catenin, a non-modification of p53 expression, a reduction of proinflammatory cytokine levels and a decrease of inflammatory protein overexpression.