Our goal is to develop a more effective and safety anti-cancer drug for lung cancer therapy.We have previously developed a highly cancer-specific expression vector, VISA system (VP16-GAL4-WPRE integrated systemic amplifier), which can enhance the therapeutic gene amplification and allow it to selectively kill cancer cells but have virtually no effect in normal cells[1].In the current study, we extend this VISA system combining with cancer specific promoter, Survivin, which is highly expressed in many cancers but not in normal adult tissues for lung cancer targeted gene therapy.We found the VISA system can dramatically enhance the Survivin promoter activity up to 65 fold resulting an activity comparable to the CMV promoter activity in lung cancer cell lines.More importantly, the promoter activity of Survivin-VISA is highly selective, expressing primarily in lung caener cell lines, but remaining very low in normal cells.In addition, the Survivin-VISA was selectively expressed in tumor tissues in mice bearing lung cancer, while CMV promoter was non-specific as it was strongly expressed in both normal and tumor tissues in mice.The therapeutic gene, a mutant Bik (BikDD) driven by Survivin-VISA can suppressthe growth of cancer cells in vitro.This therapeutic plasmid, Survivin-VISA-BikDD also prolongs mouse survival time than CMV-BikDD in lung cancer orthotopic xenograpft models.The results indicate the Survivin-VISA-BikDD associates with strong tumor suppression activity in animal model and may warrant future clinical trials for lung cancer.