With stringent regulations regarding the toxic ions selenium and arsenic on wastewater discharge, various industries such as coal mining and power generation are demanding more efficient and effective treatment methods to remove these two ions. Since the performance of commercially available thin film composite nanofiltration (NF) membranes reported so, far has a great room for improvement, a thin-film nanocomposite (TFN) NF membrane comprising polyhedral oligomeric silsesquioxane (POSS) with high efficiency was developed for the concurrent removal of selenium and arsenic from aqueous solutions. The resultant NF membrane has a mean effective pore diameter of 0.65 Am, a molecular weight cutoff of 302 Da, and superior pure water permeability of 5.4 LMH/bar with notably high rejections of SeO32-, SeO42-, and HAsO42- toward 93.9%, 96.5%, and 97.4%, respectively. The TFN membranes also exhibit slightly higher rejection performance when a mixed ion solution separation test was conducted. To the best of our knowledge, this is the first reported NF membrane comprising POSS in the selective layer for the concurrent removal of Se and As ions. The promising results achieved in this study provide promising methodology for the development of novel NF membranes to remove other multiple toxic ions from waste streams.