Because of the importance of androgens to prostate cancer (PCa) development, several candidate genes along androgen pathway have been under intensive study. Given the role of the molecular chaperone HSP70 in the regulation of the androgen receptor (AR) transactivation function, we first chose to explore the association between the HSP70-hom functional genetic variant (+2437 T > C) and prostate cancer risk by genotyping DNA samples from 101 unselected PCa patients and 105 healthy men. There was a trend towards lower frequency of TC and CC genotypes among patients when compared with healthy controls, however the difference did not reach the statistical significance (TC genotype: OR = 0.53, P = 0.05; CC genotype: OR = 0.42, P = 0.16). Moreover, individuals carrying at least one C allele have a statistically significant lower susceptibility for PCa (OR = 0.51 (0.26-0.97); P = 0.02). Since some factors may influence tumor progression rather than initiation, we also examined the relationship between the HSP70-hom polymorphism and the clinical characteristics of the malignancy at the time of diagnosis. The stratified analysis of the genotypes with the clinical stage and tumor grade showed that there was no significant difference in the risk estimates according to prognostic indicators of PCa disease in our population study. This is the first report on the studies of HSP70 SNPs in PCa and our data suggest that this genetic variant may be a genetic marker for PCa susceptibility in Tunisians.