Objective: To investigate the expression of VEGF-C and MMP-9 in colorectal cancer and their clinical significance. Methods: The expressions of VEGF-C and MMP-9 in the tissue chips (110 cases of colorectal cancer tissues and 20 cases of adjacent normal intestinal tissues) were detected by immunohistochemical staining. Results: The positive rates of VEGF-C and MMP-9 in colorectal cancer tissues were 82.7% and 80.0% respectively, which were significantly higher than those in the adjacent intestinal tissues (5.0% and 10.0%) (both P<0.05). The positive rates of VEGF-C and MMP-9 in Dukes C/D stage of colorectal cancer were 90.7% and 88.9% respectively, which were significantly higher than those in Dukes A/B stage (73.2% and 69.6%) (both P<0.05). There was a low positive correlation between the positive expression of VEGF-C and MMP-9 in the colorectal cancer tissues (r=0.253, P<0.05). Conclusion: The expressions of VEGF-C and MMP-9 are closely related to the development and invasion of colorectal cancer. Also, a high level expression of them indicates a high degree of malignancy of colorectal cancer.