The expression of chemokine receptor CXCR3 has been associated with tumor dissemination and poor prognosis in breast cancer patients. However, it is still unclear whether CXCR3 can be used as an independent molecular marker for predicting the prognosis of colonrectal carcinoma (CRC) patients. In this study, we found that the relative level of CXCR3 mRNA expression in primary colorectal cancer tissues was significantly higher than that in corresponding non-tumor colon tissues. CXCR3 protein expression was also detected in 98 of 112 primary CRC patients. Thus, CXCR3 might play a vital role in the progression of colorectal cancer. By analyzing the correlation between clinicopathological factors of patients and expression of CXCR3 protein, we showed that high level of CXCR3 protein expression was significantly associated with tumor differentiation, tumor size, lymph node metastasis, distant metastasis, and Dukes’ classification, but not with other factors of CRC patients including gender, age, tumor location and tumor invasion. Furthermore, patients with high CXCR3 expression showed poorer overall survival than those with low CXCR3 expression. Univariate and multivariate analysis indicated that the status of CXCR3 protein expression might be an independent prognostic marker for CRC patients. Therefore, CXCR3 is an indicator of a poor prognosis and a promising target for cancer therapy in colorectal cancer.