In this study, we assessed the presence of polymorphic variant rs8073069 of the BIRC5 gene....Treatment regimens were as follows: cisplatin with vinorelbine (60.6%), cisplatin with pemetrexed (24%), and cisplatin with gemcitabine (15.4%)....The presence of a homozygous GG genotype was associated with a higher risk of progression after two cycles of chemotherapy (GG vs. CG or CC: 28.9% vs. 11.9%, p = 0.0204) and with a higher risk of OS shortening (medians: 236 vs. 472 days; p = 0.0066). In a multivariate analysis, we showed that the GG genotype was independently associated with a higher risk of PFS shortening (OR = 1.92, 95% CI: 1.15–3.24, p = 0.0136), as well as OS shortening (OR = 3.63, 95% CI: 2.05–6.43, p < 0.0001)....According to our study, the rs8073069 SNP of the BIRC5 gene can be a useful marker in predicting treatment outcome in NSCLC patients.