Abstract Photodynamic therapy (PDT) is a promising cancer treatment modality that involves the interaction of the photosensitizer, molecular oxygen and light of specific wavelength to destroy tumor cells. To improve efficacy of PDT, the efforts are underway to develop combination protocols. Selenium is an essential trace element and has anticarcinogenic properties on a various human cancer model. The aim of this study was to investigate the synergetic anti-tumor effects of PDT plus selenium in vitro and in vivo. To compare the anti-proliferative effects by PDT, Selenium, or PDT plus selenium, MTT assay, microscopic observation and FACS analysis were performed. Apoptosis signaling pathways were analyzed using mouse signal transduction pathwayRT profiler PCR array (Superarray). For the vivo study, when tumor size was approximately 8 to 10 mm, Radachlorin (10mg/kg b.w.) was injected in to the tail vein at 3 hrs before irradiation with 100 J/cm2 of light and then selenium (1ug/kg b.w) was administrated daily during 20 days. Our results demonstrate that combination of selenium with PDT strongly inhibits growth of TC-1 cell and tumor in TC-1 cell implanted mice when compared to the other groups. Moreover, PDT and selenium treatment in TC-1 cells had apoptosis features in microscope and FACS analysis. Increased apoptosis was associated with tumor inhibition in the combination therapy group. In signal transduction pathway Superarray, genes closely relate to NFkB, p53, and phopholipase C pathway such as vcam1, mdm2, and fos were very significantly down-regulated at least 10 fold in TC-1 cell following co-treatment of PDT and selenium. Furthermore, anti-apoptosis related genes and tumor-promoting genes, birc2, birc3, hk2, ccl2, ptgs2, wisp1, mmp10 and wisp1 were also significantly down-regulated. Up-regulated genes by co-treatment of PDT and selenium had relatively low ranges of fold change than fold range of down-regulated genes and were related with cell survival and proliferation mechanism. These data indicate that combination therapy of selenium and PDT could more effectively induce tumor suppression response compared to PDT or Selenium alone. We suggest that combination therapy using PDT and selenium can be a useful to for inducing synergistic anticancer effect. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 496.