BACKGROUND AND STUDY AIMS:We aim to determine the frequency of thymidylate synthase (TS) and excision repair cross-complementation group 1 (ERCC-1) immunohistochemical (IHC) expression and its relationship with clinicopathologic variables in colorectal carcinoma (CRC) patients. In addition, we aim to assess the correlation between TS and ERCC-1 expression and the response of these cases to oxaliplatin and 5-fluorouracil chemotherapy (FOLFOX). PATIENTS AND METHODS:Fifty-one CRC patients were prepared for IHC analysis of ERCC-1 and TS protein expression. All patients received oxaliplatin and 5-fluorouracil combined chemotherapy (FOLFOX) and were followed up for 24 months. RESULTS:The data analysis showed that high ERCC-1 and TS expression was significantly associated with early treatment failure (P=0.020 and 0.000). In contrast, TS immunoexpression affects the disease-free survival rate (P=0.010). The presence of deep tumor invasion, distant metastasis, lymph node metastasis, and high Dukes' classification were significantly statistically associated with early treatment failure (P=0.001, 0.000, 0.041, and 0.015, respectively). CONCLUSIONS:Our results showed that both ERCC-1 and TS are predictive factors for early treatment failure in CRC patients. TS protein is a prognostic factor for disease-free survival rates. This supports the theory that both ERCC-1 and TS can be used to improve chemotherapeutic outcomes in CRC patients. High expression of TS and ERCC-1 helps in the identification of cases that will get fewer benefits from FOLFOX chemotherapy. As an innovative strategy, in these cases, we can use alternative chemotherapeutic regimens or add an extra agent. In addition, Dukes' classification and lymph node metastasis are predictive factors for early treatment failure. Thus, all those values can be used to predict CRC patients with bad prognosis and those who will get fewer benefits from FOLFOX.