This research targeted the preparation of new sepiolite-based nanocomposites and sulfonated polysulfone and compare them as desalination dense membranes. At the first step, a polysulfone with appropriate molecular weight was synthesized by condensation polymerization. The hydrophilic nature of the synthesized polymer was improved using two different methods: addition of various percentage (0.5–5% by weight) of sepiolite nanorods into the polymeric matrix, and introduction of sulfonated groups with 35–45 wt% sulfonation content to the polysulfone main chain. Precipitation by solvent evaporation was used to produce dense membranes after casting polymer solutions. FTIR, 1HNMR, and EDAX were used to identify the chemical structures of polysulfone, related nanocomposites, and sulfonated polysulfone. Also, the prepared samples were evaluated by equilibrium volume fraction of water, contact angle, water absorption, density, SEM, TGA, DSC, AFM and tensile test. Finally, the operation tests of the membrane including water flux, sodium chloride rejection, hydraulic water permeability, and salt permeability were investigated.