Previous study suggests the sensitivity to TRAIL therapy was not closely associated with the expression levels of TRAIL receptors in some types of cancer.25 We found here that rotenone was able to increase DR4 and DR5 mRNA transcripts, protein expression and surface expression, furthermore, silencing of DR4 and DR5 expression in A549 cells led to significant suppression of cell apoptosis induced by TRAIL plus rotenone. The gene discussed is TNFSF10; the disease is cancer.