Fouling control is the most critical concern in the implementation of nanofiltration (NF) for dye wastewater treatment. In this study, integration of NF and Fenton-like advanced oxidation was realized by tailoring a thin film composite NF membrane (TFNi) with in situ synthesized PDA/MnO2 interlayer. TFNi was optimized by controlling the amount of MnO2 nanoparticles incorporated within the interlayer which endowed the membrane with self-cleaning property. Besides it improved the membrane surface hydrophilicity and optimized the water transport path, resulting in alleviated fouling risks and an enhanced water permeance of 24 ± 2 L m−2 h−1 bar−1 compared to the control membrane. Fouling and subsequent chemical cleaning experiments were carried out on TFNi under various water chemistry conditions to elucidate the underlying mechanisms governing the self-cleaning properties. Accordingly, a high flux recovery ratio (FRR) (above 95%) was maintained thanks to the generation of free radicals by MnO2–H2O2 system which was validated by determining the free radical scavenging activities. Moreover, the interlayer confined radicals can facilitate the decomposition of foulants on TFNi. Conclusively, H2O2-initiated self-cleaning of TFNi can be of great prospect for the efficient treatment of dye wastewater via in-situ generated free radicals.