The efficacy of Withania somnifera on immunomodulation was tested in experimental azoxymethane induced colon cancer in mice. Azoxymethane is a potential carcinogen to induce the colon cancer in Swiss albino mice. Azoxymethane 15 mg/kg body weight was injected intraperitoneally once a week for 28 days. The colon cancer was confirmed by the appearance of aberrant crypt foci (ACF) in the colons of the experimental mice. The progression in colon tumor development was correlated with the appearance of the histological biomarker and ACF. Azoxymethane induced colon cancer animals were treated with 400 mg/kg body weight of W. somnifera extract once a week for four weeks orally. After the experimental period, the animals were sacrificed and analyzed for immunocompetent cells, immune complexes and immunoglobulins. W. somnifera significantly altered the level of leucocytes, lymphocytes, neutrophils, immune complexes and immunoglobulins (Ig) A, G and M. The azoxymethane induced colon cancer and immune dysfunction was better controlled by W. somnifera. These results suggested that the immunomodulatory effects of W. somnifera could be useful in the treatment of colon cancer.