Carica papaya (papaya), belongs to family of Caricaceae, is a perennial plant originating from the southern part of Mexico. Carica papaya leaf juice has been used to treat various diseases, including infectious diseases and cancer. However, its anticancer and associated molecular mechanism of CPE extract remains unclear. The aim of the present study is to examine the in vitro and in vivo anticancer effect of aqueous leaf extract of Carica papaya against prostate cancer. In vitro study, we used CPE to treat prostate cancer LNCaP, DU145 and PC-3 cells. CPE treatment (5, 10, 25µl/ml) for 24 hrs and 48 hrs significantly reduced cell proliferation and induced cell death in prostate cancer cells. Furthermore, we found that CPE induced G1, S, G1 as well as G2M arrest in respectively LNCaP, DU145, and PC-3 cells. At molecular level the cell cycle arrest was associated with decreased expression of cyclin-dependent kinase (CDK) 4, cyclin D1, cyclin B1, and PCN. CPE treatment induced cell death was associated with the depolarization of mitochondrial membrane potential, an increased in the expression level of Bax/Bcl2 protein ratio, cleaved caspase 3 and Poly(ADP-ribose) polymerase. CPE treatment also reduced mitochondrial fission and induces mitochondrial fusion by down regulate the level of Drp1 protein. In, addition we observed that CPE treatment up-regulated the expression of E-cadherin and down-regulate the expression of N-cadherin and vimentin. In vivo study we check the cytotoxic effect of leaf extract in C67BL/6J mice. Here. we found that orally administration of CPE did not show any significant difference in body weight, water consumption and food intake as compared to control group . Together, these findings suggest that CPE has therapeutic option for the prevention and treatment of prostate cancer.