EMMPRIN/CD147 has been proved to be associated with tumor invasion and metastasis in various human malignancies. In the present study, we investigated the expression of CD147 and its association with disease-free survival of colorectal cancer patients. CD147 expression was investigated in 328 cases of colorectal cancer by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of CD147 expression with disease-free survival of colorectal cancer patients. CD147 expression was proved to be increased in colorectal cancer (P < 0.001) and related to tumor invasion (P < 0.001), metastasis (P < 0.001), and TNM stage (P < 0.001). Kaplan-Meier showed CD147 was associated with disease-free survival of patients with colorectal cancer for patients with higher CD147 expression tend to have shorter disease-free survival (P < 0.001). Multivariate analysis also proved CD147 to be an independent prognostic factor for disease-free survival of colorectal cancer patients (P < 0.05). These results suggested the potential role of CD147 in relapse of human colorectal cancer. It might be a novel molecular marker to predict relapse of patients with colorectal cancer.