Two-dimensional (2D) materials membranes have gained widespread attention for their unique structure and outstanding separation performance. Herein, we developed a 2D vermiculite nanofiltration (TiO2@VMT) membrane using TiO2 nanoparticles as versatile intercalator. The interlayer spacing of vermiculite nanosheets was tuned from 1.352 ± 0.002 nm to 1.424 ± 0.004 nm. As a result, the optimized TiO2@VMT membrane exhibited high water flux of 261 L m−2 h−1, which was 14 times higher than that of vermiculite membrane, simultaneously showed excellent rejections (>98 %) for various organic dyes (molecular weight >374 g mol−1). Due to the photocatalytic degradation ability of TiO2 nanoparticles towards organic foulants, the TiO2@VMT membrane possessed excellent anti-fouling performance, with a flux recovery rate exceeding 90 % under UV radiation after three cycles of filtration experiment using oil-in-water emulsion and BSA solution as model foulants. Accordingly, our work may offer a possible route for the development of 2D nanofiltration membrane for efficient water purification.