BACKGROUND: The beneficial effects of selenium (Se) to human health are exerted by selenoproteins, which can be quantified in blood and used as biomarkers of Se status. Different responses of Se biomarkers after supplementation with selenomethionine and sodium selenite have been observed and some of them could be due to genetic polymorphisms, mainly single nucleotide polymorphisms (SNPs). Brazil nuts are known to be the richest natural source of Se. OBJECTIVE: Investigate how genetic variations in selenoprotein genes modulate biomarkers of Se status in response to Brazil nut supplementation. METHODS: The SU.BRA.NUT study was a four month interventional trial which involved healthy volunteers of both genders, selected in University of Sao Paulo. The supplementation was done with one Brazil nut a day for 8 weeks, followed by 8 weeks of washout. Blood samples were collected at 5 time points: baseline, 4 and 8 weeks of supplementation and 4 and 8 weeks of washout for analysis of five biomarkers of Se status - erythrocyte GPx1 (Glutathione Peroxidase 1) activity, plasma GPx3 activity, plasma Se, erythrocyte Se, and plasma selenoprotein P. The gene expression of GPX1, SELENOP, SELENOF and SELENOS was done before and after 8 weeks of supplementation. The volunteers were genotyped for SNPs in GPX1 (rs1050450, rs3811699 and rs1800699), GPX4 (rs713041), SELENOP (rs3877899 and rs7579), SELENOF (rs5845) and SELENOS (rs34713741). RESULTS: A total of 130 volunteers finished the protocol. The concentrations of four biomarkers of Se status increased significantly after 4 and 8 weeks of supplementation, being modulated by gender. In addition, erythrocyte GPx1 activity was associated with rs1050450, rs713041 and rs5845. Plasma Se was associated with rs7579 and selenoprotein P with plasma Se at baseline. Nut supplementation significantly increased GPX1 mRNA expression only in subjects with CC genotype at rs1050450. SELENOP mRNA expression was significantly lower in subjects with GG genotype at rs7579 before and after supplementation. CONCLUSION: Genetic variations in GPX1 and SELENOP genes are associated with different responses of molecular and biochemical biomarkers of Se status after Brazil nut supplementation in healthy Brazilians. The SU.BRA.NUT study was registred at www.clinicaltrials.gov as NCT 03111355.