Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressiveproperties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. Toexplore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent controltissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibodyindicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as comparedto the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed thedown regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association(p<0.05) with the histological type and tumor invasion properties of the cancer. Our data demonstrated thatloss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significantinsights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for coloncancer.