Objective To explore the diagnostic significance of ratio of free prostate specific antigen to total prostate (fPSA/tPSA), prostate specific antigen density (PSAD), and prostate specific antigen transition zone density (PSATZ) in serum prostate specific antigen (PSA) gray area for prostate cancer (PCa).Methods A total of 173 cases with PCa and benign prostatic hyperplasia (BPH) whose tPSA levels were 4-10 ng/mL were selected in the study. Serum fPSA and tPSA were detected, and fPSA/tPSA ratio was calculated. Prostate volume was determined by transtectal ultrasound. PSAD and PSATZ were calculated.The diagnostic significance of fPSA/tPSA, PSAD, and PSATZ in PSA gray area for PCa were analyzed using Python 3.5 software.Results The PCa patients’ and the BPH patients’ fPSA/tPSA ratios were 0.17±0.072 and 0.2±0.085 respectively.Their PSADs were (0.25±0.11) μg/L and (0.14±0.054) μg/L respectively. Their PSADTZs were (0.53±0.31) μg/L and (0.25±0.14) μg/L respectively. The two groups showed significant differences in the above three indicators (P<0.05). The sensitivity of fPSA/tPSA and PSAD for PCa reached 79%.Conclusion Both PSAD and PSATZ in PSA gray area can increase sensitivity in the diagnosis of PCa. Moreover, fPSA/tPSA, PSAD, and PSADTZ are of great value for the diagnosis of PCa.