XPC, XPD, XPF, and XPG genes are implicated in the nucleotide excision repair (NER) system. Gene polymorphisms in NER repair system may influence the individual's capacity to recognize and repair DNA lesions, thus increasing the cancer risk. We hypothesized that these gene polymorphisms might influence the probability of developing acute myeloid leukemia (AML). We investigated the XPC, XPD, XPF, and XPG gene polymorphisms in 108 AML cases and 163 healthy controls. Also cytogenetic analyses besides FLT3 and DNMT3A mutations status were investigated. We found that variant genotypes (heterozygous and homozygous) of XPD 2251A > C and 22541A > C and the heterozygous genotype of XPG 3507G > C were associated with the risk of developing AML (OR = 2.55; 95% CI = 1.53-4.25; p value <0.001; OR = 1.66, 95 % CI = 1.02-2.72; p value = 0.047, and OR = 2.36; 95 % CI = 1.32-4.21; p value = 0.004, respectively). No association was found between white blood cell counts, FLT3, DNMT3A mutations, cytogenetic risk group, and variant genotypes of none of the analyzed polymorphisms. Variant homozygous XPF 673C > T genotype was associated with higher dose of cytosine arabinoside treatment administrated to AML patients (p value = 0.04). No differences were found regarding survival time and variant genotype in the investigated gene polymorphisms with the exception of XPD 2251A > C. In conclusion, XPD 22541A > C, XPD 2251A > C, and XPG 3507G > C gene polymorphisms confer susceptibility to AML, while XPC 2920A > C, XPF-673C > T, XPF 11985A > G are not associated with AML.