Growing evidence indicates the involvement of a genetic component in prostate cancer (CaP) susceptibility and clinical severity. Studies have reported the role of germline mutations and single nucleotide polymorphisms (SNPs) ofTP53as possible risk factors for cancer development. In this single institutional retrospective study, we identified common SNPs in theTP53gene in AA and CA men and performed association analyses for functionalTP53SNPs with the clinico-pathological features of CaP. The SNP genotyping analysis of the final cohort of 308 men (212 AA; 95 CA) identified 74 SNPs in theTP53region, with a minor allele frequency (MAF) of at least 1%. Two SNPs were non-synonymous in the exonic region ofTP53: rs1800371 (Pro47Ser) and rs1042522 (Arg72Pro). The Pro47Ser variant had an MAF of 0.01 in AA but was not detected in CA. Arg72Pro was the most common SNP, with an MAF of 0.50 (0.41 in AA; 0.68 in CA). Arg72Pro was associated with a shorter time to biochemical recurrence (BCR) (p= 0.046; HR = 1.52). The study demonstrated ancestral differences in the allele frequencies of theTP53Arg72Pro and Pro47Ser SNPs, providing a valuable framework for evaluating CaP disparities among AA and CA men.