Cancer is still one of the most invasive health problems around the world although many researches have been done in this field. Different kinds of drugs are developed and used to improve cancer therapy. Some evidence has shown that nonsteroidal anti-inflammatory drugs (NSAIDs) have anticancer activity in addition to anti-inflammatory effects. To improve the safety profile of NSAIDs and enhance anticancer potency, different strategies such as hybridization are used in several studies. Indomethacin is a lead compound in NSAIDs classes' demonstrated inhibitory activity for some malignancies including breast and ovarian cancer. Two kinds of hybrids were proposed and synthesized using diamine linkers via amid bonds: indomethacin-indomethacin (hybrid A) and indomethacin-methotrexate (MTX; hybrid B). To confirm the structures of newly synthesized hybrids, melting points, IR, H NMR were applied. The cytotoxic effects of synthesized hybrids against Hela and MCF-7 cancer cells were evaluated by MTT assay. The results showed that both hybrids were more cytotoxic than indomethacin and MTX alone.