Tumor suppressive properties have been identified in the mammalian sterile cell line, 20 like kinase-1 (MST-1) and the role they may have in prostate cancer (PCa) has yet to be elucidated due to the paucity of reports. The goal of this study is to investigate the expression and the potential role of MST1 in the development and progression of PCa. The expression level of MST1 in PCa was analyzed by immunohistochemistry (IHC), qPCR and western blotting, and the clinicopathological parameters of PCa patients underwent statistical analysis. MST1, vascular endothelial growth factor (VEGF), androgen receptor (AR), and neuron-specific enolase (NSE) proteins were analyzed by western blot. A cell counting kit, CCK-8 assay and a transwell migration assay were used to assess the proliferation and migration capacity of C4-2 cells. Human umbilical vein endothelial cells, (HUVECs) were used in a tubule formation assay to evaluate prostate cancer angiogenesis. The results of this study documents that the expression level of MST1 is downregulated in PCa and the downregulation closely correlates with the metastatic status of patients. (p < 0.05). Overexpression of MST1 significantly inhibits C4-2 cells' proliferation and migration. In addition, overexpression of MST1 significantly inhibits VEGF, AR, NSE expression, and the angiogenesis of PCa. This study suggests that MST1 downregulation may play a role as a tumor suppressor gene in the pathogenesis and progression of prostate cancer. MST1 downregulation also inhibits the neuroendocrine differentiation and the angiogenesis of early-stage prostate cancer cells.