Abstract: Objective To evaluate prognosis prediction value of CA19-9 for metastatic colorectal cancer treated by cetuximab and first-line chemotherapy. Methods Seventy-eight patients with wild-type RAS metastatic colorectal cancer receiving cetuximab plus FOLFOX4 or FOLFIRI chemotherapy in our hospital from June 2012 to June 2017 were included in our study, and the relationship between serum CA19-9 and RECIST criteria throughout the treatment course was analyzed. Furthermore, Kaplan-Meier curve was applied to analyze the progression-free survival (PFS) of patients with normal baseline CA19-9 level (n=30) and patients with elevated baseline CA19-9 level (n=48). Results Compared with the RECIST standard, the sensitivity and specificity of CA19-9 to evaluate the disease control rate (DCR) were 87.7% and 70.6%, and positive predictive value and negative predictive value were 86.5% and 72.7%, with an accuracy of 82.2%. Patients with normal baseline CA19-9 level had longer PFS than those with elevated CA19-9 levels (9.40 months vs 7.45 months, P=0.010). Conclusion Our results highlight the importance of CA19-9 in assessing the efficacy of cetuximab combined with first-line chemotherapy and predicting the prognosis of patients with metastatic colorectal cancer.