Aim of the study. To elucidate the association of allelic variants of single nucleotide polymorphism in NRF2 (rs6726395, 177238501A>G) and TLR9 (rs352162, 52218953T>C) genes, each gene separately and in their com bination, with peculiarities of the course of critical conditions during lung infection. Materials and methods. DNA from 86 post-operative patients and oncologic patients was genotyped in an allele specific fashion using tetra-primer polymerase chain reaction followed by gel electrophoresis analysis of products. Results. It has been found that septic shock patients with NRF2 177238501A>G GG genotype had increased mortality and higher APACHE II score and developed non-responsive edema more frequently. Patients with NRF2 177238501A>G GG/TLR9 52218953T>C CC genotype combination developed septic shock and nosocomial pneumonia more rarely. Conclusion. The homozygous NRF2 177238501A>G (GG) allele combination is unfavorable for the course and outcome of critical conditions only in combination with TLR9 52218953T>C СT or TLR9 52218953T>C TT alleles in septic shock patients. At the same time, the combination of TLR9 52218953T>C СС alleles in the same patients with ‘unfavorable’ NRF2 177238501A>G GG protects against development of septic shock and nosoco mial pneumonia. © 2016, V.A. Negovsky Research Institute of General Reanimatology. All Rights reserved.