The study of individual human sensitivity to adverse environmental factors is important for predicting pathology risk and developing preventive measures. Of particular concern are factors capable of disrupting genetic structures in human cells. Comparison of genotoxic effects of chemicals in the somatic cells of the same donors in vivo and in vitro makes possible to elucidate the applicability of such in vitro model for predicting individual sensitivity to genotoxicants and identifying high-risk groups. The aim of the study is a comparative study of the sensitivity of human somatic cells to the genotoxic effects of pesticides in vivo and in vitro. The micronucleus test on buccal epithelial cells of humans contacted with pesticides in the spring-summer season due to professional exposure and the DNA comet assay on human peripheral blood lymphocytes with and without a metabolic activation were used. Before blood sampling for in vitro assessment, the study participants (48 persons) had not been exposed to pesticides at least for 3 months). A study of the ability of captan, thiram, and chlorpyrifos to induce DNA damage in vitro showed statistically significant dose-dependent genotoxic effects (based on the "% DNA in the tail comet" parameter). The levels of DNA damage in lymphocytes from different donors varied in the range of 4-20 times. A group of donors was identified whose lymphocytes were more sensitive to the DNA-damaging effects of pesticides. The micronucleus test in vivo showed statistically significant differences in the level of cytogenetic damages in the epithelial cells of different donors. Сomparisson of the abnormalities observed in buccal epithelial cells in the micronucleus test and the levels of DNA damage in the lymphocytes in the DNA comet assay revealed the comparable results in the in vivo and in vitro systems. Donors whose lymphocytes showed the maximum DNA-damaging effect of pesticides also had a high risk level based on the index of accumulation of cytogenetic damage. Epithelial cells of individuals whose lymphocytes were tolerant to the action of pesticides in the model test system showed a low level of cytogenetic abnormalities and a high reparation index. The in vitro test system using human lymphocytes may be a promising model for assessing individual genetic risk.