NBS1 plays an important role in the maintenance of genomic integrity, by being involved in cellular response to DNA damage. The NBS1 rs1805794 G>C polymorphism has been investigated in several studies, but its function still remains unclear due to some controversial results. The present work aimed to evaluate the role of this polymorphism in prostate cancer progression, by performing a case-control study comparing 239 patients who were diagnosed with early disease to 186 who presented advanced disease. We also assessed NBS1 mRNA expression among the different groups by quantitative real time (qRT)-polymerase chain reaction. We found that the GG carriers presented an almost two fold increased risk for advanced prostate disease (odds ratio [OR] = 1.87; confidence interval [CI] = 1.26-2.79; p = 0.002). Further, high tumor grade (OR = 3.02; CI = 2.32-3.92; p<0.001) and high serum prostate specific antigen (PSA) (OR = 6.48; CI = 4.48-9.38; p<0.001) were consistently associated to advanced disease. Regarding NBS1 mRNA expression, we did not find any association with the different outcomes nor genotypes (p = 0.926; p = 0.894, respectively). Our results suggest for the first time that rs1805794 GG genotype appears to be associated with a higher risk for advanced prostate cancer, thus, suggesting a possible new role for NBS1 in prostate cancer progression.