Objective: To analyze the relationship between serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) levels and pathological features in colorectal cancer patients. Methods: Forty-one cases each of colorectal cancer and health checkups in our hospital were selected from October 2018 to October 2022, and were divided into the colorectal cancer group and the healthy control group. serum AFP and CEA levels were detected in both groups. Compare the serum AFP and CEA levels between the colorectal cancer group and the healthy control group; compare the serum AFP and CEA levels between the colorectal cancer group with different tumor stages, different different degrees of differentiation, different tumor diameters, and different prognoses; and analyze the correlation between the AFP and CEA and the tumor stage, differentiation, tumor diameter, and prognosis of death. Results: Serum AFP and CEA levels were higher in the colorectal cancer group than in the healthy control group (P < 0.05). Serum AFP and CEA levels were higher in patients with colorectal cancer stage III-IV than in patients with stage I-II (P < 0.05). Serum AFP and CEA levels were higher in patients with low differentiation of colorectal cancer than in patients with middle differentiation and high differentiation (P < 0.05). Serum AFP and CEA levels were higher in patients with colorectal cancer tumor diameter ≥5cm than in patients <5cm (P < 0.05). Serum AFP and CEA levels were higher in patients who died of colorectal cancer than in patients who survived (P < 0.05).Pearson analysis showed that AFP and CEA were positively correlated with tumor stage, tumor diameter, and prognosis of death, and negatively correlated with the degree of differentiation (P < 0.05). Conclusion: Serum AFP and CEA levels were high in colorectal cancer patients, and there was a significant association between AFP and CEA expression levels and colorectal cancer pathologic features and prognosis.