Background <p>Prostate cancer (PCa) is one of the leading causes of morbidity and mortality among men worldwide. While age, race and family history are established risk factors, their molecular underpinning remain poorly understood. Aberrant promoter methylation is a well-known mechanism for silencing tumor suppressor genes in PCa. This study evaluates the methylation status of glutathione-S-transferase-P1 (GSTP1) and adenomatous polyposis coli (APC) genes in Moroccan men with PCa, assessing their potential as biomarkers for early detection and tumor characterization.</p> Methods <p>A total of 70 prostate cancer tissue samples and 50 control tissues were analyzed. Methylation specific PCR (MSP) was used to evaluate the promoter methylation status of GSTP1 and APC, The results were correlated with age, PSA levels, Gleason score, tumor stage, and life style factors.</p> Results <p>GSTP1 promoter methylation was observed in 79% of PCa cases and was significantly associated with lower Gleason scores (= 6: 64%, <i>P</i> = 0.006) and early T-stages tumors (T1 and T2, <i>P</i> = 0.002). APC methylation was found in 63% of cases and showed a significant association with higher Gleason scores (&gt; 6: 59%, <i>P</i> = 0.007). Although APC methylation did not significantly correlate with pathological T-stage, it was more frequent in early stages (T1: 45%, T2: 34%). No significant associations were observed between GSTP1 or APC methylation and age, PSA levels, smoking, or alcohol consumption.</p> Conclusion <p>promoter methylation of GSTP1 and APC is frequent in Moroccan prostate cancer patients. GSTP1 methylation appears to be associated with early stage disease, Whereas APC methylation is linked to tumor aggressiveness. These findings suggest the potential utility of GSTP1 and APC promoter methylation as biomarkers for prostate cancer detection and characterization, further validation with larger cohorts and gene expression analysis is needed to confirm their clinical relevance.</p>