Objective To investigate the expression of EphA8 in colon cancer and its clinical significance.Methods Real-time quantitative polymerase chain reaction (RT-PCR) and Western blot were respectively used to assess the expressions of EphA8 mRNA and protein in normal colon mucosa cell line and colon cancer cell lines.Immunohistochemistry for EphA8 and vascular endothelial growth factor (VEGF) were performed in 98 cases of colon cancer and 12 matched normal mucosa tissues.CD31 immunohistochemical staining was used for microvascular density (MVD) counting.The relationships between the expression of EphA8 and the expression of VEGF and MVD,the clinical pathological significance,and the prognosis of patients were analyzed by statistical methods.Results EphA8 mRNA expressions were significantly higher in colon cancer cell lines than those in normal mucosa cell line (t =11.98,13.54,P ＜0.001).EphA8 protein expressions were significantly higher in colon cancer cell lines than those in normal mucosa cell line (t =4.63,P =0.006;t =4.92,P =0.004).The high expression of EphA8 was closely related to tumor size (x2 =22.97,P＜0.001),TNM stage (P＜0.001),differentiated degree (P =0.007)and lymph node metastasis (P＜0.001),distant metastasis (x2 =6.97,P =0.008) and poor survival rote (x2 =17.3,P ＜0.001).But it was not associated with the gender and age (x2 =1.36,P =0.30; x2 =0.83,P=0.44).Besides,EphA8 had positive correlation with the VEGF and MVD (r =0.434,P ＜0.001; r =0.584,P ＜0.001).Conclusion EphA8 may play important roles in the development and metastasis of colon cancer,which has potential clinical values in the therapeutic intervention and prognosis of colon cancer.