In the subgroup analysis by histological type and chemotherapy treatment, XPC rs2229090 GC/CC exhibited a significant association with a longer PFS, while ERCC4 rs1799798 GA genotype was significantly associated with a shorter OS in 477 adenocarcinoma patients, but not in 138 squamous cell carcinoma patients, suggesting a potential histological difference in genetic regulation of lung cancer survival outcome in response to the treatments. Here, XPC is linked to adenocarcinoma.