Lycopene is a natural compound that alleviates oxidative stress and inflammation, exerting therapeutic effects in a number of cancers. The aim of this study is to investigate the efficacy of lycopene in inhibiting prostate cancer. Cell viability assays indicated the dose- and time-dependent toxicity of lycopene in prostate cancer cells. Annexin V/propidium iodide double-staining assays revealed the strong apoptotic effects of lycopene. The levels of inflammatory factors, including interleukin-1 (IL1), IL6, IL8, and tumor necrosis factor-alpha (TNF-alpha), in lycopene-treated cells were also reduced by lycopene treatment. With the increasing dose of lycopene, the survival of mice bearing prostate cancer xenografts was significantly improved (P < 0.01), and the tumor burden was significantly reduced (P < 0.01). Our results indicate that lycopene is a promising chemotherapy drug, which inhibits prostate cancer progression by suppressing the inflammatory response.