Variation of individuals’ DNA repair capacity has been linked to cancer susceptibility.The xeroderma pigmentsum group F (XPF) plays a pivotal role in nucleotide-excision repair (NER) pathway.This study was to examine the functional significance of XPF promoter polymorphisms and their association with lung cancer risk.The function of XPF promoter polymorphisms was tested by a set of biochemical assays,and their effects on lung cancer risk were determined by a case-control analysis of 988 patients with lung cancer and 986 controls.The XPF-673T allele showed a significantly higher transcriptional activity as compared with the-673C allele.The-673TT genotype was associated with a decreased risk of lung cancer compared with the CC genotype (adjusted OR=0.62,95% CI=0.42-0.91;P=0.015) and this effect was more significant among males (adjusted OR=0.55,95% CI=0.35-0.86;P=0.009),elder subjects (adjusted OR = 0.51,95% CI = 0.30-0.86;P= 0.012),and light smokers (adjusted OR = 0.35,95% CI =0.144).88;P=0.026).These findings suggest that functional polymorphisms influencing DNA repair capacity may confer susceptibility to lung cancer.