Background: Endothelin-1 and Endostar are both significant for the progression, proliferation, metastasisand invasion of cancer. In this paper, we studied the effect of ET-1 RNAi and Endostar in PC-3 prostatic cancercells. Materials and Methods: The lentiviral vector was used in the establishment of ET-1 knockdown PC-3 cells.Progression and apoptosis were assessed by CKK-8 and flow cytometry, respectively. Transwell assay was usedto estimate invasion and signaling pathways were studied by Western blotting. Results: ET-1 mRNA and proteinin ET-1 knockdown PC-3 cells were reduced to 26.4% and 22.4% compared with control group, respectively.ET-1 RNAi and Endostar both were effective for the suppression of progression and invasion of PC-3 cells.From Western blotting results, the effects of ET-1 regulation and Endostar on PC-3 cells were at least relatedto some signaling pathways involving PI3K/Akt/Caspase-3, Erk1/2/Bcl-2/Caspase-3 and MMPs (MMP-2 andMMP-9). Furthermore, combined treatment of ET-1RNAi and Endostar was found to be more effective thansingle treatment. Conclusions: Both ET-1 RNAi and Endostar can inhibit the progression and invasion of PC-3cells, but combined treatment might be a better therapeutic schedule.