Abstract: Objective：To investigate the expression of EphA1 in colorectal cancers and its clinical significance. Methods ：Quantitative real-time RT-PCR and immunohistostaining were employed to detect the expression level of EphA1 in colon cancer cell lines and CRC specimens.Methylation specific PCR (MSP) was also performed. Results ：The expression of EphA1 transcript, methylated DNA of EphA1 was detected in cell lines.EphA1 mRNA expression in the corresponding normal mucosae is not significantly different from that in tumor tissues （P=0.496).In adenomas, the immunostaining for EphA1 was positive diffusely and strongly.However, in CRCs, the expression of EphA1 protein was predominately down-regulated.Reduced or lost expression of the EphA1 protein was significantly associated with poor differentiation （P=0.027), greater depth of wall invasion （P=0.002) and advanced TNM stage （P=0.002), and preferentially occurred in patients with lymph node metastasis （P=0.019).Patients with reduced EphA1 expression had a tendency of poorer prognosis than those with EphA1 upregulation.ConcolusionEphA1 may have tumor suppressor roles in CRCs and may be an important biomarker by which malignancy, biological behavior and prognosis are evaluated.