Objective To explore the significance of P504s, P63, PSMA, and Ck34βE12 in the identification of benign and malignant prostate lesions.Methods A total of 112 surgical resection specimens of transrectal ultrasound guided prostate biopsy were collected from the Traditional Chinese Medicine Hospital of Heze City of Shandong Province from January 2014 to December 2016.All specimens were prepared for paraffin section and detected for P504s, P63, PSMA, and Ck34βE12.According to the proportion of positive cells, the detection Results were classified as follows.The accuracy, sensitivity, and specificity of P504S, P63, PSMA, and Ck34βE12 detected separately and jointly in the diagnosis of prostate cancer were compared.Results The positive rate of P504s in prostate cancer patients was 100.00%, and the dispersion positive rate was up to 62.75%, significantly higher than those in the AAH, BCH, and BPH patients.The positive rates of P63 and Ck34βE12 in prostate cancer patients were both 0%, while those in the HGPIN, AAH, BCH, and BPH patients were all 100.00%.The positive rates of PSMA in prostate cancer and HGPIN patients were 98.04% and 90.91%, respectively, while those in the AAH, BCH, and BPH patients were 13.33%, 11.11%, and 9.52%, respectively.The accuracy, sensitivity, and specificity of combined detection of P504s, P63, PSMA, and Ck34 reached 100.00%, 97.85%,and 98.24%, respectively, showing clinical diagnostic value.Conclusion For the diagnosis of prostate cancer, combined detection of P504s, P63, PSMA, and Ck34βE12 could significantly increase the accuracy, sensitivity, and specificity.