Oxadiazoles have received much attention due to their wide range of biological activities including antitumor activity. In this study, we aimed to study apoptotic effects of some 1,3,4-oxadiazole derivatives on human lung adenocarcinoma (A549) and rat glioma (C6) cell lines. The cytotoxicity of the compounds on both cell lines was determined, and the effects of these compounds on DNA synthesis were measured. Compounds 2 and 6 which exhibited significant cytotoxic activity in MTT assay were chosen for flow cytometric analyses to determine apoptotic percent of cells. These compounds also exhibited better DNA synthesis inhibition activity on cancer cells. Compound 6 carrying 2,4-dichlorophenyl substituent exhibited the highest apoptotic effect on A549 cells via the induction of Caspase 3 activity. It was suggested that compounds 2 and 6 can be identified as the most promising anticancer agents against A549 and C6 cancer cell lines.