Abstract: To address the costly and long-chain treatment of saline mine water for hardness removal and desalination, hollow fiber nanofiltration (NF) membranes of H-N80 and H-N90 were assessed for Na⁺/Ca²⁺ rejection and selective separation, and a short process of dual-section NF was simulated. Pure water permeabilities were 1.44×10⁶ and 4.2×10⁵ L/(m²·h·Pa) (14.4, 4.2 L/(m2·h bar)) for H-N80 and H-N90, with Ca²⁺ rejection both > 70% and partial Na⁺ ions permeation. Under optimized conditions as working pressure P = 5×10⁵ Pa and feed flow rate Q = 7.1 L/min, Na⁺/Ca²⁺ separation factors were found as 3.4 and 2.6 for H-N80 and H-N90, governed by both steric and Donnan effects. Membrane flux and desalination rate declined with increasing feed salinity (from 3 700→17 000→51 000 μS/cm). Despite a larger MWCO ( H-N80: 400 Da vs H-N90: 200 Da), H-N80 exhibited an initial rise then drop in cation rejection, whereas H-N90 declined continuously along with higher salinity. Positive-charge modification is proposed as the reason enhancing H-N80 membrane’s rejection to Na⁺ and Ca²⁺ via adsorption-and-capture interlayer mechanism. With treatment capacity of 100 m³/h and water recovery of 75%, modeling calculations indicated that hollow-fiber configured NF-NF process reduced energy consumption by 75% and membrane area by 30% in comparison to the typical spiral-wound NF. The combined hollow-fiber NF process is expected to replace the conventional long processes of “chemical softening – high-density clarifier – multi-media filtration – membrane separation”, thereby achieving for process integration and efficiency improvement for large-scale underground treatment of mine water.