The aim of this study is to evaluate the predictive value of carbohydrate antigen125 (CA125) and carcino embryonic antigen (CEA) expression and its guiding role of choosing chemotherapy regimen in post-operation patients with colorectal carcinoma.The clinical data of all patients, including laboratory data and pathological data, were collected from the electronic medical records. Kaplan-Meier Log rank test, COX regression model and subgroup analyses were employed to assess the correlation between the expression of CA125 and CEA in patients with colorectal carcinoma and the survival, and the effect on chemotherapy efficacy.Kaplan-Meier showed that CA125 expression is negatively related to the progression-free survival (PFS) of the post-operative patients, Median PFS was 1140 days in the patients with high expression, and Median PFS was 1387 days in the patients with low expression (χ = 4.715, P = .030); CEA expression is also negatively associated with the PFS of the post-operative patients, Median PFS was 1197 days in the patients with high expression, and Median PFS was 1424 days in the patients with low expression (χ = 4.992, P = .025). Subgroup analysis also showed that the patients with normal CA125 and CEA had better prognosis, median PFS was 1505 days, and the patients with CA125 and (or) CEA high expression had poor prognosis and median PFS was 1162 days (χ = 13.346, P = .001), and found that there was no statistical difference in patients with oxaliplatin plus capecitabine (XELOX) and oxaliplatin, 5-fluorouracil and Calcium folinate (FOLFOX) chemotherapy in patients with CA125 and CEA low expression. However, in these patients with CA125 or (and) CEA high expression, the median PFS of patients treated with XELOX was 1082 days, and the median PFS of patients treated with FOLFOX chemotherapy was 1335 (χ = 4.547, P = .033).Expression of CA125 and CEA associated with the survival of patients, and have some guiding significance for chemotherapy in patients with colorectal cancer after operation; Compared with XELOX, FOLFOX chemotherapy is more effective for CA125 or (and) CEA high expression patients with colorectal carcinoma.