Background and Objectives: Prostate cancer (PCa) is one of the most common cancer types in men and recognized as the fifth cause of death globally. Human paraoxanase-1 (PON1) is an enzyme synthesized in the liver and linked with high-density lipoprotein (HDL). The current study aimed to evaluate the association between PCa and PON1 enzyme polymorphism in Egyptian patients. Subjects and methods: A total of 100 persons. Fifty patients diagnosed as PCa patients (group I) along with fifty non-PCa (group II) of matchable age were enrolled in this study. Patients with another type of cancer or any chronic disease were excluded. Prostate-specific antigen (PSA) was assayed in all subject's study by using ELISA Kit Protocol (Cat. No.: EK-310-19); in addition to CBC, hematological parameters (hemoglobin, total leucocyte count, and platelets count) were estimated by using an automated hematology analyzer (Pentra 80) according to manufacturer's instructions. PON1 Q192R gene polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: PON1 (Q192R) gene polymorphism showed QR genotype in PCa patients (group I)  ]32(64%)[ compared with non-PCa (group II)] 4(8%)[. The association between PON1 (Q192R) gene polymorphism with prostate cancer group and PSA were statistically significant (P value= 0.000). Hemoglobin showed a significant association with PCa patients (group I) and PSA (P = 0.000), while total leucocyte count and platelet count showed non-significant when compared with the control group. Conclusion: Such findings showed that PON1 (Q192R) gene polymorphism could be associated with prostate cancer and disease growth. Recommendation, furthermore comprehensive stud­ies are required to confirm the role of PON1 gene polymorphism in the etiology of PCa.