Survivin, an anti-apoptotic protein, is abundantly expressed in a variety of cancer cells, including hepatoma cells, resulting in the resistance of these cells to various apoptotic stimuli. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known to induce cancer cell-specific apoptosis, but hepatoma cells are resistant to TRAIL-induced apoptosis. In the present study, we have examined whether the downregulation of survivin by short interfering RNA (siRNA) promotes spontaneous or TRAIL-induced apoptosis in Huh-7 human hepatoma cells. Survivin siRNA transfection downregulated the expression of survivin in Huh-7 cells and reduced cell viability by 20% through inducing spontaneous apoptosis. TRAIL (1 to 2 ng/ml) only slightly induced apoptosis in Huh-7 cells; however, survivin siRNA transfection apparently enhanced TRAIL-induced apoptosis. These results suggest that the level of survivin is linked to the susceptibility of Huh-7 cells to TRAIL. It is possible that survivin downregulation by siRNA combined with TRAIL administration may provide a new therapeutic strategy against hepatoma.