PURPOSE: Curcumin, a potential chemopreventive agent, was found to inhibit cancer cells in S/G2M phases of the cell cycle, when radiation is more effective. The purpose of the current study was to investigate whether curcumin can sensitize squamous cell carcinoma (SCC) cells to the ionizing effects of irradiation. METHODS: Curcumin (3.5 μM) was added for 48 hours to an SCC cell line prior to irradiation. Cell growth (counts) and colony-formation (colonogenic assay) were examined after radiation. RESULTS: Incubation with curcumin only (3.75 μM) for 48 hours did not decrease the number of cells or the ability to form colonies in the absence of radiation. However, in plates that were exposed to 1-5 Gy of radiation, cell counts dropped significantly if pretreated with curcumin with a maximal effect at 2.5 Gy (where the cell counts dropped from 1240 to 1017, P < 0.001). The colonogenic assay revealed a significant decrease in the ability to form colonies following pretreatment with curcumin in all radiation doses (P < 0.05). CONCLUSIONS: Given the appropriate doses, curcumin exhibits radio-sensitizing effects on SCC cells in vitro.