Objective: To investigate the adjunctive role of some peripheral blood parameters to serum prostate specific antigen (PSA) in predicting the patients with prostate cancer (PCa) prior to prostate biopsy, and clinically significant PCa among those. Material and Methods: This prospective study included men aged ≥45 years, who were scheduled to undergo a prostate biopsy due to gray-zone PSA levels. The levels of free and total PSA (fPSA and tPSA), total testosterone (TT), PSA density (PSAD), C-reactive protein (CRP), De Ritis ratio (aspartate aminotransferase/alanine transaminase) and hemograms were recorded. Patients were divided into 2 groups as benign prostatic hyperplasia (Group 1) and PCa (Group 2) groups. The PCa group was further divided into 2 subgroups as clinically significant and clinically insignificant PCa. The pre-biopsy values of the variables were compared between the groups. Results: A total of 210 patients were included in the study (Group 1, n=105; Group 2, n=105). The mean age was 65.1±7.4 years, the mean tPSA level was 6.14±2.05 ng/mL, and the mean TT level was 15.46±5.47 nmol/L. Age, prostate volume, the values of fPSA, PSAD, CRP, and the ratios of fPSA/tPSA, CRP/albumin and De Ritis were statistically different between the groups. In the PCa group, only the tPSA level was significantly different between the subgroups (p=0.005). The area under curve and the cut-off value for tPSA to predict clinically significant PCa were 0.669 and 5.8 ng/mL, respectively. Conclusion: CRP, the CRP/albumin ratio and De Ritis ratio may further help predict a diagnosis of PCa.