Prostate cancer (PCa) is one of the most common cancer types worldwide in men. Although Growth Arrest DNA Damage-Inducible 45 (GADD45) family members, GADD45α , GADD45β and GADD45γ , are responsible for the activation of several molecules in certain cellular pathways affecting cell fate, including tumorigenesis, as stress sensors, the role of GADD45γ in PCa is still not clear. In this study, our aim was to detect the methylation and protein expression profiles of GADD45γ in benign prostate hyperplasia (BPH) (60 patients) and PCa (56 patients). The methylation of GADD45γ was determined by methylation-sensitive high resolution melting analysis. Immunohistochemistry was used for evaluating GADD45γ protein expression. The methylation frequency for GADD45γ was as low as 1.8% in PCa compared with BPH (P=0.000). GADD45γ protein was overexpressed in PCa cases (53.6%) compared with the BPH cases (33.3%), and the difference was statistically different (P=0.028). There was no correlation between GADD45γ methylation and protein expression in both groups. This study shows that in contrast to hematological malignencies, GADD45γ methylation is not one of the common epigenetic changes in PCa. In addition, we suggest that the loss of important regulatory mechanisms involved in GADD45γ might play a role in the pathogenesis of BPH.