Purpose: This study aimed to evaluate the clinical significance of p53 and Ki-67 expressions in patients with colorectal cancer. Methods: Immunohistochemical expressions of p53 and Ki-67 in 205 patients with colorectal cancer were examined. Results were correlated with clinical and pathological parameters. Results: Overexpression of p53 was significantly associated with a proximal location of the tumor (P=0.031) and with lymph node involvement (P=0.030) however, Ki-67 expression was not correlated with any of the clinicopathological variables. Positive p53 staining was significantly associated with a higher level of Ki-67 (P=0.009). Conclusion: Overexpression of p53 was strongly correlated with lymph node metastasis in colorectal cancer; thus, p53 may be used as a possible prognostic marker in patients with colorectal cancer.