Abstract: Objective To understand the mutation status of Ras（K-Ras／N-Ras），BRAF，PIK3CA and its associations with clinicopathological characteristics in colorectal cancer（CRC）. Methods Tumor specimens were collected from 200 CRC patients treated in Peking University Cancer Hospital from December 2013 to October 2014. The mutation status of Ras，including K-Ras（exon 2，3 and 4），N-Ras（exon 2，3 and 4），BRAF（exon 15）and PIK3CA（exon 9，20）were detected by direct sequencing. The relationships between the gene mutations and clinicopathological parameters were analyzed. Results Ras mutations were found in 92（46.0％）of 200 patients，including 87 cases（43.5%）of K-Ras，of which occurred mainly in exon 2，and 5 cases of N-Ras. One patient carried KRas mutation and N-Ras mutation simultaneously. BRAF mutations were found in 15 patients（7.5％）and all types of BRAF mutation were V600E. K-Ras and BRAF mutations were mutually exclusive. PIK3CA mutations were found in 9 patients（4.5％），which appeared simultaneously in Ras／BRAF mutation tumors. Also，the mutation rate of Ras（K-Ras／N-Ras）in patients ≥65 years was higher than that in patients ＜65 years（P＜0.05）. Other clinicopathological features，such as gender，location of the tumor，histological classification，tumor differentiation，TNM staging，local lymph node metastasis，distant metastasis, and post-operative recurrence and metastasis had no relationship with Ras（K-Ras／N-Ras）gene mutations（P＞0.05）. BRAF／PIK3CA mutation rates were higher in right side colon tumors（P＜0.05）. No significant associations were observed between BRAF／PIK3CA mutations and gender，age，histological classification，tumor differentiation，TNM staging，local lymph node metastasis, distant metastasis, and post-operative recurrence and metastasis（P＞0.05）. Conclusion N-Ras／PIK3CA genes were rarely mutated in Chinese CRC patients. K-Ras／N-Ras mutation were associated with age，while BRAF／PIK3CA mutation were only associated with location of the tumor. Combined detection with K-Ras，N-Ras，BRAF and PIK3CA gene in colorectal cancer patients will provide more reliable basis for clinical targeted therapy.