© 2018 Frontiers in Bioscience. All rights reserved. In the United States, Prostate Cancer (PCa) is the leading cause of cancer-related mortality in men. PCa resulted in abnormal growth and function of prostate gland such as secretion of high level of gamma-seminoprotein (gama-SM)/Prostate-Specific Antigen (PSA) which could be detected in the blood. Beside gama-SM protein, the levels of heat shock proteins (Hsp70) were also observed significantly high. Therefore, gama-SM and Hsp70 are unique proteins with high potential for PCa therapeutics and diagnostics. High level of Hsp70 suppresses apoptosis, thus allowing PCa cells to exist; however, depletion of Hsp70 induces apoptosis in PCa cells. Gama-SM is the most prominent biomarker for PCa screening; however, its accuracy is still questionable. Thus, a more suitable streamline biomarker for PCa screening is urgently needed. Hsp70 and gama-SM proteins could be used as a revolutionary biomarker for PCa, and could help to identify possible therapeutic target(s). In this review article we will discuss the relationship between the Hsp70 and gama-SM proteins with PCa, their potential as a dual biomarker, and the possibility for both proteins being used as therapeutic targets.