Our study evaluated 163 individuals, being 74 soybean farmers, occupationally exposed to pesticides, and 89 individuals from Goias municipalities, Central Brazil, with similar conditions to the exposed group, comprising the control group. Of the 74 soybean farmers, 43 exposed directly to pesticides and 31 exposed indirectly. The exposed group consisted of individuals aged 19 to 63 years, 21 women and 53 men, and the control group had ages ranging from 18 to 64 years, being 36 women and 53 men. 18.9% of the exposed group were poisoned by pesticides, and the most common symptoms were headache and gastrointestinal problems. The genotype frequencies of the rs2031920 (T>C) polymorphism in the CYP2E1 gene present significant differences between the exposed and control groups (p = 0.02), showing that 24.3% of the exposed group were heterozygotes against 6.7% in the control group. For the OGG1 gene, two SNPs, rs1052133 (G>C) and rs293795 (T>C), were evaluated and the genotype frequencies were not statistically different between the exposed and control groups. The DNA damage was distinct (p < 0.05) in the three analyzed comet parameters (tail length, Olive tail moment, %DNA) between groups. However, there was no influence of age and alcohol consumption between the groups associated with the polymorphisms in the CYP2E1 and OGG1 genes and DNA damage. We also did not find altered hematological and biochemical parameters in the exposed group. Thus, this pioneering study at Goias State carried out an overview of the health of soybean farmers. We evaluated classic laboratory exams, associated with exposure markers (comet assay) and susceptibility markers (genetic polymorphisms), emphasizing the need to expand the Brazilian health assessment protocol. We found, in soybean farmers, increased DNA damage and a higher number of heterozygotes in CYP2E1 gene, compared with the control group, despite the lack of association with age, educational level, smoking, drinking habits, and genetic polymorphisms.