The prostate specific antigen (PSA) as a biomarker for prostate cancer (PCa) diagnosis has been widely used in the clinic for several decades. However, PSA has a low specificity for PCa diagnosis, thereby several gene, blood and urine-based biomarkers (such as sarcosine) underlying biology of PCa progression are being developed to improve the accuracy of PCa diagnosis. In the present review, we focus on novel PCa biomarkers, which are ptentially superior to PSA in PCa screening and facilitate clinical PCa diagonosis. The early PCa screening with reliable biomarkers is critical in reducing the mortality of clinical PCa (high-risk PCa). For clinical insignificant PCa (low-risk PCa) patients and benign prostatic hyperplasia patients, biopsies should be avoided and disease progression should... be monitored by using non-invasive biomarkers.