We have designed and analyzed a novel (to the best of our knowledge) two-beam interference lithography system for large-area (wafer-level) nanopatterning with enhanced tunability of pattern periodicities. The tunable feature has been achieved by placing two rotational mirrors in the expanded beam paths at regulated angles for a desired period. Theoretical analyses show that the effective pattern coverage area greater than a $4\mathrm{in}\mathrm{.}$ ( $10\mathrm{cm}$ ) wafer scale is attainable with a $325\mathrm{nm}$ ( $30\mathrm{cm}$ coherence length) HeCd laser and $4\mathrm{in}\mathrm{.}$ ( $10\mathrm{cm}$ ) mirrors, while the pattern coverage area is restrained by the overruling effects between the optical coherence and mirror size. The experimental results also demonstrate uniform nanopatterns at varying periods ( $250–750\mathrm{nm}$ ) on $4\mathrm{in}\mathrm{.}$ ( $10\mathrm{cm}$ ) substrates, validating the theoretical analyses. The tunable two-mirror interferometer will offer a convenient and robust way to prepare large-area nanostructures on a wafer scale with superior tunability in their pattern periodicities.