PROL4 (proline-rich protein 4) was screened out in lung cancer cells for its defective expression in our previous study. By transfection of PROL4 into lung adenocarcinoma cell line LTEP-a-2, a stable cell strain was acquired. It was shown that in PROL4 expressing cells, compared to the vector control cells, the serum dependence of cell growth was markedly enhanced, soft agar colony-forming ability was suppressed. The tumor growth was also significantly restrained by PROL4 in vivo experiments. Furthermore, PROL4 transfected cancer cell strains were found to display an elevated sensitivity to cisplatin treatment than mock-transfectant control cells, and the sensitivity up-regulation was closely related to the rate of cell apoptosis induced by PROL4 and cisplatin cooperately. These results suggest that PROL4 is potentially a new genetic engineering target to enhance the chemotherapeutic effects of cisplatin in lung cancer treatment.