Abstract: Objective: To investigate the application value of normalized apparent diffusion coefficient (ADC) values and prostate-specific antigen density (PSAD) in category 3 Prostate Imaging Reporting and Data System (PI-RADS) version 2.1 lesions when the serum prostate-specific antigen (PSA) level is in the grey zone of 4～10ng/mL. Methods: From January 2018 to June 2022, 58 patients with PI-RADS v2.1 scores of 3 and PSA values of 4.0–10.0 ng/mL were selected. According to the pathological results, the patients were divided into the PCa (20 cases) and non-PCa (38 cases) groups. The clinical data of the patients were collected, including age, PSA, prostate volume (PV), and PSAD (PSA/V) calculated by formula. Meanwhile, the ADC values of the lesion area and the normal tissue in the peripheral zone were measured on the ADC image, and the standardized apparent diffusion coefficient value was calculated, namely ADCn (ADC lesion/ADC peripheral zone). Statistical software was used to determine the statistical significance of the differences of ADCn and PSAD between the two groups. Receiver operating characteristic (ROC) curves were used to compare the diagnostic efficacy of the two for PCa in lesions with PI-RADS v2.1 score of 3. Results: Age and PSA did not differ significantly between the two groups. Compared to the non-PCa group, the PCa group showed lower ADCn (0.52 vs. 0.69) and higher PSAD (0.28 vs. 0.18). The area under the ROC curve (AUC), sensitivity, and specificity of ADCn and PSAD in the diagnosis of PCa were 0.849, 85.2%, and 81.6 % and 0.813, 85.0%, and 78.4%, respectively. For an optimal diagnostic threshold of 0.373, the AUC, sensitivity, and specificity of PCa were 0.962, 90.0%, and 89.5%, respectively. Conclusions: ADCn and PSAD can assist in PCa detection in lesions category 3 PI-RADS v2.1 lesions in the PSA gray area. The combination of ADCn and PSAD can significantly improve the diagnostic sensitivity and specificity.