Mammalian target of rapamycin (mTOR) is associated with gene transcription, protein translation and initiation, the synthesis of ribosomes, and apoptosis. The down regulation of mTOR induces apoptosis in malignant tumor cells. Elemene, a sesquiterpene from the traditional Chinese medicinal herb Curcuma wenyujin, is active against a wide range of tumor types. In the present study, decreasing the expression of mTOR with mTOR small interfering RNA (siRNA) increased the toxicity of elemene and irradiation against hypoxic lung adenocarcinoma A549 cells. The results showed that transfecting mTOR siRNA into A549 cells significantly decreased the expression of hypoxia-inducible factor 1α (HIF-1α) and survivin. Compared to control cells, cells transfected with mTOR siRNA that were hypoxic exhibited increased apoptosis. Overall, the expression of HIF-1α and survivin proteins decreased following treatment with elemene and irradiation and after transfection with mTOR siRNA. Apoptosis was higher in transfected than in untransfected cells treated with elemene and/or irradiation.