Objective:To investigate the relationship between polymorphisms of DNA repair gene XPD751 and sensitivity to Gemcitabine/Cisplatin(GP) chemotherapy in advanced non-small-cell lung cancer(NSCLC). Methods:116 patients with NSCLC were analyzed. All patients were treated with GP chemotherapy,and DNA of peripheral blood leukocytes was obtained before therapy. XPD751 genotypes were detected by PCR-RFLP method. Results:①Of all cases,the frequencies of XPD751 Lys/Lys,Lys/Gln and Gln/Gln genotype were 81.0%,17.2% and 1.8%,respectively. The overall response rate of chemotherapy in all patients was 37.9%. ② The response rate of chemotherapy among patients with XPD751 Lys/Lys,Lys/Gln and Gln/Gln genotypes were 39.4%,25.0%,100.0%,respectively,and no significant difference was found(χ2 = 4.775,P = 0.093). Comparing to patients with Lys/Gln genotypes,GP chemotherapy showed no significant superior effect in patients with Lys/Lys genotypes,adjusted for gender,age,clinical stage and cytology type(OR=1.09,95%CI:0.95~1.51)-③The incidence rate of vomiting/nausea and alopecie in Lys/Lys genotype was significantly higher than other genotypes(χ2 = 4.032,P = 0.045;χ2 = 4.344,P = 0.037). Conclusion:The polymorphisms of the XPD751 might not be associated with the clinical response to GP chemotherapy in advanced NSCLC,but could be used as a marker of toxicity prognosis.