Purpose: The chemokine receptors CCR7 and CXCR4 have been shown to play an important role in cancer invasion and metastasis. This study was aimed to investigate CCR7 and CXCR4 expressions and evaluate the association between their expressions and the clinicopathological features in gastrointestinal cancer. Method: 27 paired tissue samples from patients who had curative surgery for gastrointestinal cancer were obtained. Quantitative real-time PCR, immunochemistry assay and western blot analysis were carried out to investigate the expressions of CCR7, CXCR4 expressions in gastrointestinal cancer. Results: The cancer tissues expressed significant higher level of CCR7 (P = 0.000) and CXCR4 (P = 0.000) protein than the adjacent normal mucosa. Expressions of CCR7 (P = 0.002) and CXCR4 (P = 0.003) protein in cancer tissues exhibited significant correlation with differentiation in gastrointestinal cancer. Conclusion: Expressions of CCR7 and CXCR4 protein were associated with differentiation in gastrointestinal cancer. CCR7 and CXCR4 may be predictive factors for poor prognosis in patients with gastrointestinal cancer.