The chemotherapeutic drug doxorubicin (Dox) is prescribed for cancer treatment. In addition to cancer cells, its cytotoxic effect affects healthy tissues with a high proliferation index, such as the testes. This study examined the potential of selenium nanoparticles (SeNPs) to attenuate Dox-induced testicular apoptosis. Thirty-two male albino rats were divided into four experimental groups (n=8): Control (group I), Dox (group II), SeNPs (group III) and Dox + SeNPs (group IV). For four weeks, Dox (3 mg/kg body weight) was administered intraperitoneally weekly, while SeNPs (0.5 mg/kg) were administered orally daily. After experimental treatments, testicular tissues were harvested for histological, immunohistochemical and molecular analyses. SeNPs treatment with Dox (group IV) markedly decreased testicular histological lesions induced by Dox (group II) and up-regulated (p<0.05) the defensive antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) genes. SeNPs also decreased (p<0.05) the protein levels of pro-apoptotic P53, Bax, caspase-3 and increased (p<0.05) antiapoptotic Bcl-2 genes in group IV compared to group II. To conclude, SeNPs alleviate Dox-induced testicular damage and apoptosis by improving the antioxidant capacity of spermatogenic cells and by inhibiting apoptosis.