To evaluate the joint effect of nine single nucleotide polymorphisms for three DNA repair genes in the region of chromosome 19q13.2-3 on susceptibility of lung cancer in a Chinese population, we conducted a hospital-based case-control study consisting of 247 lung cancer cases and 253 cancer-free controls matched on age, gender and ethnicity. Associations between the haplotypes and susceptibility of lung cancer were tested. The global test of haplotype association revealed a statistically significant difference in the haplotype distribution between cases and controls (global test: chi(2)=60.45, d.f.=15, P=2.11E-07). The two haplotypes were underrepresented among cases (Hap5 defined by ERCC1118(A)-ERCC2156(C)-ERCC2312(G)-ERCC2751(A)-XRCC1194(T)-XRCC1206(A)-XRCC1280(G)-XRCC1399(G)-XRCC1632(G) and Hap12 defined by ERCC1118(G)-ERCC2156(C)-ERCC2312(G)-ERCC2751(A)-XRCC1194(C)-XRCC1206(A)-XRCC1280(G)-XRCC1399(A)-XRCC1632(G)). Three of the haplotypes were overrepresented among cases (Hap3 defined by ERCC1118(A)-ERCC2156(C)-ERCC2312(G)-ERCC2751(A)-XRCC1194(C)-XRCC1206(A)-XRCC1280(G)-XRCC1399(G)-XRCC1632(G), Hap4 defined by ERCC1118(A)-ERCC2156(C)-ERCC2312(G)-ERCC2751(A)-XRCC1194(C)-XRCC1206(G)-XRCC1280(G)-XRCC1399(G)-XRCC1632(A), and Hap10 defined by ERCC1118(G)-ERCC2156(A)-ERCC2312(G)-ERCC2751(A)-XRCC1194(T)-XRCC1206(A)-XRCC1280(G)-XRCC1399(G)-XRCC1632(G)). Haplotypes 3 and 10 (cases=5.7%, controls=1.0%, OR=6.56, 95%CI=1.83-23.54, P=0.001; cases=13.3%, controls=5.6%, OR=2.73, 95%CI=1.51-4.94, P=0.0006) were the most strongly associated with increased lung cancer risk. There was considerable linkage disequilibrium exists between SNPs both within genes and between genes in the region. The two blocks for solid spine of LD and six htSNPs were found. The haplotype analysis suggested that the biologically effective polymorphisms co-segregate with some of the haplotypes. This result supports the hypothesis that the sub-region is important for lung cancer susceptibility. Haplotype studies using larger study groups will be required to obtain conclusive results.