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AIM: To detect the expression of COX-2 and HER-2 in colorectal cancer and to analyze their correlation and clinical significance.METHODS: A total of 1026 colorectal cancer surgical specimens were collected from patients treated fromDecember 2002 to December 2007 at the First Affiliated Hospital of Anhui Medical University. All specimens were made into 4-μm slices. The expression of COX-2 and HER-2 were detected by immunohistochemistry using the streptavidin-biotin-peroxidase method. The correlations between COX-2 and HER-2 expression and colorectal cancer clinical features were analyzed.RESULTS: The positive rates of COX-2 and HER-2 expression in colorectal cancer were 77.97%(800/1026) and 46.20%(474/1026), respectively. There was a significant correlation between COX-2 and HER-2 expression in colorectal cancer(P < 0.05). In patients with tumor size ≥ 5 cm, the positive rates of COX-2 and HER-2 expression were 81.48%(308/378) and 57.94%(219/378), respectively. In patients with serosal invasion, the positive COX-2 and HER-2 expression rates were 80.53%(612/760) and 49.21%(374/760), respectively. In patients with lymph node metastasis, the positive expression rates were 85.04%(506/595) and 54.62%(325/595), respectively, and the positive expression rates differed significantly between patients with lymph node metastasis and those without(P < 0.05). In patients with Duke’s C and D colorectal cancer, the positive COX-2 and HER-2 expression rates were 82.80%(443/535) and 57.94%(310/535), respectively. In patients with poorly differentiated colorectal cancer, the positive expression rates were 74.49%(210/282) and 52.84%(149/282), respectively(P < 0.05). In patients with distant metastasis, the positive expression rates were 82.27%(116/141) and 53.90%(76/141), respectively(P < 0.05). These findings suggest that COX-2 and HER-2 have synergistic effects in colorectal cancer. COX-2 and HER-2 expression had no significant correlation with sex, age, or tumor location. CONCLUSION: COX-2 and HER-2 are important markers for invasion and metastasis of colorectal cancer, and they act together to regulate the invasion and metastasis of colorectal cancer.