Hematological toxicities (HTs) in lung cancer (LCa) may compromise the delivery of Radio-Chemotherapy (RTCT), and consequently affect the control of the disease. The aim of this study is to evaluate the association of Single nucleotide polymorphisms (SNPs) with HT.In this prospective multicentre study, 264 patients with primary LCa treated with RTCT between 2012 and 2018 were included. Genotyping analysis was performed on DNA isolated from peripheral blood samples by real-time polymerase chain reaction (PCR) using TaqMan. HTs were scored using the Common Toxicity Criteria (CTCAE) version 5.0.An increased risk of HT ≥ grade 2 was observed in patients with the GG genotype of the SNP rs7459185 (HSPβ1) with a hazard ratio (HR) of 1.462 (95 %CI 1.054-2.029, p = 0.007). Similarly, those patients had an increased risk of overall HT ≥ grade 3 with a HR of 1.531 (95 %CI 1.016-2.30, p = 0.007). The patients with the GG genotype experienced an acute lymphopenia ≥ Grade 3 (HR 1.590 [95 %CI 1.004-2.517; p 0.045]) and acute anemia ≥ Grade 2 (HR 1.886 [95 %CI 1.060-3.356; p 0.032]), compared to the GC/CC genotypes.Our findings show a relationship between the functional GG genotypic of the SNP rs7459185 (HSPβ1) and heightened risk the development of HT, including anemia and lymphopenia in patients with LCa. This genetic variant could be utilized as a predictive marker to tailor treatment intensity, contributing to the advancement of individualized therapeutic approaches.