Objective: To investigate the relations of CA19-9 and CEA levels with clinicopathological features and prognosis of patients with colorectal cancer. Methods: The clinicopathologic data of 356 patients with colorectal cancer undergoing radical surgery from January 2007 to July 2008 were collected. The relations of preoperative CEA and CA19-9 levels and clinicopathologic features and postoperative survival rate of the patients were analyzed. Results: Results of univariate analysis showed that the increased serum CEA level was related to depth of tumor invasion, lymph node metastasis, histological type, liver metastases, peripheral organ involvement (all P<0.05). and the increased serum CA19-9 level was associated with depth of tumor invasion, peritoneal metastasis, and liver metastasis (all P<0.05). Results of survival analysis indicated that survival rate in patients with increased serum CEA level was lower than that in those with normal serum CEA level (P<0.05); survival rate had no statistical difference between patients with increased serum CA19-9 level and normal serum CA19-9 level (P>0.05); survival rate in patients with both increased CEA and CA19-9 levels showed no statistical difference compared to those with increased serum CEA or increased serum CA19-9 level (both P>0.05), but was significantly lower than in those with both normal serum CEA and CA19-9 levels (P<0.05). Conclusion: Simultaneously increased levels of both CEA and CA19-9 is likely related to a late-stage event in colorectal cancer, which suggests an unfavorable prognosis for the patients.