Abstract: Objective To investigate the relationship between the emergence of KRAS mutations and the acquired resistance of metastatic colorectal cancer after treatment with cetuximab, and discuss the follow-up treatment strategy. Methods A retrospective analysis of clinical data about 1 patient (female, 70 years old) with K-RAS wild metastatic colorectal cancer after administration of cetuximab on November 15, 2014 in No.2 department of oncology in Chinese PLA General Hospital was performed and related literatures were reviewed. Results After administration of cetuximab for 43 months, the K-RAS gene mutations could be detected in the liver metastasis focus in the patient. Then, the patient was administrated with bevacizumab plus oxaliplatin. According to the RESICT Solid Tumors evaluation criteria, stable disease was observed in the patient. Conclusion The present study shows that early treatment with MEK inhibitors can significantly delay and reverse the resistance of cetuximab.