Abstract: Objective To investigate the value of the 12th codon of K-Ras gene mutation detection in the serum exosomes instead of the tumor tissues in patients with colorectal cancer. Methods The peripheral blood samples of 90 patients pathologically diagnosed as locally advanced or metastatic colorectal cancer from May 2014 to September 2015 in our hospital were collected. The serum exosomes were extracted by ExoQuick agent. Exosomes and blood cells were extracted by salting out method. The 12th codon of K-Ras gene was amplified by PCR， and the mutation was detected by next generation sequencing. The specificity of serum exosomes DNA and blood cell DNA mutations was compared. Mutations of 12th codon of K-Ras gene were compared between exosomes and histological detection. Results Among 90 cases with colorectal cancer， 43 cases of the 12th codon mutation in K-Ras gene were detected with the mutation rate of 47.8％. Four kinds of mutation were detected， and the G12D mutation rate was the highest. Compared with histological examination， the sensitivity was 90.6％ and the consistency was 81.1％（Kappa=0.62，P＜0.05）. Conclusion The consistent of serum exosome DNA used for detection of tumor-related mutation was higher than that of tumor tissues， which can be used as a source of liquid biopsy to guide the individualized treatment of tumors.