Objective：To evaluate whether the presence of K-ras gene mutations is a useful tumor-response marker in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy. Methods：46 patients with locally advanced rectal cancer who were treated with preoperative chemoradiotherapy were enrolled. DNA was isolated from paraffin-embedded tissues before chemoradiotherapy amplified by PCR，and then sequenced in order to detect K-ras mutations in codons 12，13. Post-operative speci－mens were classified according to the Dwork’s tumor regression grading （TRG）. Good tumor regression was defined as TRG 2+3+4，insignificant tumor regression as TRG 0+1. Results：DNA was successfully extracted from 43 patients，K-ras mutation occured in 15 patients（34.9%），of which mutation in codon 12 occurred in 11 patients（73.3%），and mutation in，codon 13 occurred in 4 patients （26.7%）. 29 （67.4%） patients were graded as TRG 2+3+4，14（32.6%）as TRG 0+1. Pathologic response rates in K-ras gene muta－tion group and wild group were 66.7% and 67.8%，respectively，with no significant difference between two groups （P=0.793）. Con－clusions：There is no difference in the degree of tumor pathological regression after preoperative chemoradiotherapy for rectal cancer in the different K-ras genotypes，K-ras mutation status does not predict response to preoperative chemoradiotherapy.