Objective: To investigate the expressions of lysine-specific demethylase 1 (LSD1), E-cadherin (E-cad) and N-cadherin (N-cad) in colon cancer and their clinical significance. Methods: Cancer tissue specimens from 108 cases of colon cancer who underwent operation at Xiangya hospital from February 2006 to December 2008 were collected. The expressions of LSD1, E-cad and N-cad in these colon cancer tissues were determined by immunohistochemical staining, and their relations with clinicopathologic characteristics and prognosis of the patients were analyzed. Results: In the entire group, the positive expression rate of LSD1, E-cad and N-cad in colon was 66.7% (72/108), 85.2% (92/108) and 41.7% (45/108), respectively. Positive LSD1 expression rate was significantly increased in tumors with advanced TNM stage and distant metastasis, which for E-cad was the opposite (all P<0.05), while there were no statistical differences in N-cad expression among the groups divided according to clinicopathologic factors (all P>0.05). In colon cancer tissues, the LSD1 expression was negatively correlated with E-cad expression (r=–0.318, P=0.001), but showed no significant correlation with N-cad expression (r=0.182, P=0.06). The overall survival rate in LSD1 positive expression group and E-cad negative expression group was significantly lower than that in their respective negative expression group and positive expression group (both P<0.05), while positive or negative N-cad expression yielded no significant relation with the overall survival of the patients (P=0.410). Conclusion: LSD1 and E-cad expressions are closely related to colon cancer metastasis, and colon cancer with positive LSD1 and negative E-cad expression may herald a poor prognosis.