Introduction. Failures of neuro-immune regulation can be caused by both external exposures and polymorphisms of candidate genes, transcription genes in particular.The purpose of the study. To estimate effects of exposure to benzene and rs1042522 polymorphism of the TP53 gene on formation of the immune state and phenotype in children suffering from disorders of autonomic nervous system (ANS) (G90.8 and G90.9).Materials and methods. The study involved eighty-five children (aged 7–12 years) — 46 children exposed to benzene (blood benzene concentration > 0 μg/cm) (observation group), and 39 children not exposed to benzene (reference group) who lived in the Perm region and had disorders of ANS (the observation group was 2.1 times more likely to have a disease (p < 0.05)). CD3+CD95+, IL-4, IFN-γ and IgG to benzene were determined by immunobiologic methods. The gene polymorphism was evaluated by Real-time polymerase chain reaction.Results. Benzene contamination in the observation group was established to be equal of 0.0069 ± 0.0014 µg/cm3. The analyzed indices were shown to be different between the groups; thus, absolute CD3+CD95+ expression was 1.4 times as low and IFN-γ 1.7 times as low in the observation group against the reference one whereas IL-4 and IgG specific to benzene were 2.6 times and 2.5 times as high respectively. We found an authentic direct relationship between the level of IgG specific to benzene and IL-4 (r = 0.21; r = 0.51; p < 0.05 respectively), and an inverse relationship between IFN-γ expression (r = –0.53; p < 0.05) and blood benzene levels. The observation group showed to have significant (p < 0.05) higher frequency of the allele C and CC genotype of the TP53 rs1042522 gene, 1.4 and 1.6 times higher respectively against the reference group (RR = 1.60; CI: 1.21–2.09).Research limitations. Are related to a small sample size.Conclusion. The hypothesis regarding participation of by benzene and changed polymorphisms of the candidate gene TP53 (the allele C of the TP53 Pro72Arg gene) in creating relative risks (RR = 1.60) of immune regulation failures. This can be considered a condition for formation of a specific phenotype of ANS diseases (with more frequent manifestations of pathology signs) associated with benzene.Compliance with ethical standards. The study was approved by the local ethics committee of the Federal Scientific Center for Medical and Preventive Health Risk Management Technologies, the meeting protocol No. 5 dated February 28, 2023. All participants and their legal representatives gave informed voluntary written consent to participate in the study.Contribution of the authors: Zaitseva N.V., Dolgikh O.V. — concept, interpretation, editing of data; Yaroma A.V. — concept and design of research, analysis and interpretation of data, writing the text of the article, compiling a list of references, statistical data processing; Kazakova O.A. — data analysis and interpretation, statistical data processing. All authors have approved the final version of the manuscript and bear full responsibility for the integrity of all its parts.Funding. The research was not granted any sponsor support.Conflict of interest. The authors declare no competing interests.Received: May 14, 2025 / Accepted: June 24, 2025 / Published: October 31, 2025