Efficient lithium extraction from salt-lake brines with high Mg2+/Li+ ratios remains constrained by the permeability–selectivity trade-off of conventional polyamide nanofiltration (NF) membranes. Here, a pyridinium-based quaternary ammonium monomer, 1-(2-aminoethyl)-4-carbamoylpyridinium chloride (QAC), is rationally designed as a multifunctional aqueous-phase modifier for interfacial polymerization. QAC simultaneously regulates polyamide network formation and surface charge characteristics, enabling synergistic enhancement of transport and selectivity. Incorporation of QAC suppresses excessive crosslinking through steric effects, generating an enlarged and uniform pore structure that increases pure water flux to 176.1 L m−2 h−1, over threefold higher than that of the pristine membrane. Concurrently, permanently charged quaternary ammonium groups impart a stable positive surface potential, yielding sustained MgCl2 rejection of ∼95% and a Mg2+/Li + separation factor up to 75.4 under extreme Mg2+/Li+ ratios of 100:1. The membrane demonstrates robust pressure tolerance and long-term stability over 120 h. A two-stage nanofiltration process further reduces the Mg2+/Li+ ratio of simulated brine from 40:1 to 0.3:1, highlighting strong potential for practical lithium recovery.