It has been shown that antisense oligodeoxynucleotide (ODN) treatments provide an effective, specific approach to inhibiting the function of target proteins. Using this method, we have acquired additional evidence that protein kinase C-epsilon functions as an oncogenic protein in the progression of recurrent human prostate cancer. This chapter describes the use of antisense ODN to directly target cellular protein kinase C-epsilon as a potential chemotherapeutic agent for blocking the advance of prostatic adenocarcinoma to androgen-independence. Using Lipofectin as the carrier, phosphorothioate-modified antisense ODNs were transferred into prostate cancer cells with high efficiency, effectively inhibiting the expression of endogenous protein kinase C-epsilon and the androgen-independent (AI) proliferation of several independent human prostate cancer cell lines.