Prostate cancer is the most common type of cancer affecting males. The aim of the present study was to investigate the antitumor effect of cisplatin in combination with programmed cell death protein 5 (Pdcd5) on Du145 prostate cancer cells and to elucidate the underlying mechanisms of action. An MTT cell viability assay was performed in order to determine the proliferation rate of Du145 cells. The results demonstrated that Du145 cells treated with cisplatin for 48 h had an IC50 value >200 µM; however, following transfection of Pdcd5 in combination with treatment with various concentrations of cisplatin, the proliferation rates of Du145 and PC3 prostate cancer cells were significantly decreased in a dose‑dependent manner, with IC50 values of 114.1 and 50.6 µM, respectively. Annexin V‑fluorescein isothiocyanate/propidium iodide dual labeling analyses demonstrated a significant increase in the apoptotic rate of Du145 cells following transfection of Pcdc5 in combination with cisplatin treatment. Furthermore, western blot analysis revealed a marked increase in activated caspase‑3 expression in Du145 cells as well as a decreased ratio of Bcl‑2/Bax. In conclusion, the results of the present study demonstrated that Pdcd5 increased the chemosensitivity of prostate cancer cells and decreased the toxicity of cisplatin via activation of the receptor‑associated apoptotic pathway; this may therefore indicate the combined use of cisplatin and Pdcd5 as a novel therapeutic strategy for the treatment of prostate cancer.