Apoptosis is an important mechanism of malignant tumor formation and progression. Single nucleotide polymorphisms (SNPs) located within cell death genes may influence cancer risk. We explored the relationship between FasL -844T/C and/or Fas -1377G/A SNPs and pulmonary adenocarcinoma (AD). Two hundred seventy-five patients with pulmonary AD of South China admitted into Zhejiang Cancer Hospital from July 2007 to October 2011 were randomly selected, and their clinicopathological data were collected at the same time. Two hundred ninety-seven cases of healthy individuals were selected as control. FasL -844T/C and Fas -1377G/A SNPs were detected by PCR-RFLP technique to evaluate the relationships between these two SNPs and pulmonary AD. Age, FasL -844 and Fas -1377 SNPs were associated with increased risk of pulmonary AD susceptibility in main effect analysis. FasL -844CC and Fas -1377 AA were associated with an increased risk for the development of pulmonary AD only in age <60 years people, but not in those ≥60 years. FasL -844CC genotype was associated with an increased risk for pulmonary AD (adjusted OR = 2.010, 95 % CI 1.196-3.379, P = 0.008) compared with TT genotype. However, Fas -1377 AA was a risk factor only when FasL -844 genotype was CC. Fas -1377 genotypes showed significant effect modification of pulmonary AD risk by FasL -844 genotype with test of the interaction term adjusting for age, gender, and FasL -844 SNP. Fas -1377G/A was not associated with the clinicopathological factors, while FasL -844C/T was associated with tumor stage and lymph node metastasis in age ≥60 years people and tumor stage in those <60 years. In conclusion, FasL -844 SNP is associated with the susceptibility of pulmonary AD in age <60 years people. Fas -1377 SNP may modify the association of FasL -844 SNP with the risk of pulmonary AD. FasL -844 genotype plays an important role in the occurrence and progression of pulmonary AD.