Abstract：In order to investigate the molecular occurrence of KRAS, BRAF, and PIK3CA mutations in the colorectal cancer patients and to study the association of these events with clinicopathological parameters. Two hundred paraffn-embedded tumor specimens were collected from 150 colorectal cancer patients who underwent resection of primary tumors at Xijing Hospital of Digestive Diseases and General Hospital of Lanzhou Military Region of PLA from the year of 2008 to 2009. The DNAs are extracted from 200 cases of human colorectal cancer tissue samples. KRAS, BRAF, and PIK3CA mutations analysis is performed by PCR and pyrosequencing. Using statistical methods, the relationships between the gene mutations and clinicopathological parameters are analyzed. The KRAS point mutation rate is 32% (48/150); The V600e mutation rate of BRAF is 8% (12/150); PIK3CA point mutation rate is 12% (18/150), among them, exon 9 mutation rate is 6% (9/150) and exon 20 mutation rate is 6% (9/150). The study indicates that the mutational status of BRAF is not correlated with Dukes' staging, histological type, age, and gender of patients. However, strong connections are found between KRAS, PIK3CA mutations and Dukes' staging (staging D, 48% (9/150)).