Abstract： Background Microwaves have other biological effects on cancer as well besides killing tumor cells by coagulation.Some studies showed that microwaves may induce apoptosis in some tumor cells. The apoptotic effect of microwaves may help in clinic to remove residual malignant cells nearby the primary lesion and avoid relapse subsequently. However,there is little evidence on this subject from lung cancer. We studied the effect of microwaves on inducing apoptosis in the human lung carcinoma cell line A549 cells, aiming to identify its effect on apoptosis.Methods A549 cells were radiated by various intensities and durations of microwaves. Apoptosis induction in A549 cells was analyzed by morphological observations, tetrazolium blue color method (MTT) assays, flow cytometery,immunohistochemistry, and image analyses.Results Morphological changes in A549 cells, including cell shrinking and nuclear pycnosis, were observed after microwave radiation. Microwaves significantly inhibited metabolic activities and induced apoptosis in A549 cells. The results of the MTT assay showed a significant decrease of cell activities in all the radiation groups compared with the normal control (P ＜0.01). The low point of cell activities often appeared at 6-12 hours after radiation. Apoptosis was also confirmed by flow cytometery. The early stage apoptotic rate reached 6.10%-17.98% and the advanced stage apoptotic rate + necrosis rate reached 8.04%-44.06% at 6 hours after microwave irradiation, in contrast to 2.32% and 4.10% in the respective control groups. Down-regulation of Bcl-2 expression and up-regulation of p53 expression were observed by immunohistochemistry after radiation. In most treated groups, the down-regulation of Bcl-2 expression reached its lowest level at 3-6 hours after radiation (integrated optical density (IOD)-6 hours: 2.13±0.08-5.14±0.13 vs. control: 5.79±0.10, P＜0.01 ) and the up-regulation of P53 expression peaked at about 3 hours (IOD-3 hours: 2.61±0.13-8.07±0.11 vs. control:1.29±0.07, P ＜0.01). Cell damage, apoptosis, and protein expression levels in the samples differed depending on the radiation intensity and duration.Conclusions Microwaves can promote apoptosis in A549 cells. The effect depends on the duration and dosage of microwave radiation. Bcl-2 and p53 proteins may be involved in the apoptotic process of A549 cells induced by microwaves.