The exploitation of efficient noble metal free catalyst for nitrophenols is of great importance. Herein, 3D hierarchical N, O‐MoS2/NiO hollow microspheres have been successfully prepared via a facile hydrothermal method. Characterizations reveal that the as‐obtained hollow microspheres were assembled by amorphous N, O co‐doped MoS2 and NiO nanosheets. Catalytic experiments show that the hollow microspheres displayed remarkably enhanced catalytic activity for 2, 3, 4‐nitrophenol reduction with the kapp reaching 1.72 min−1 for 4‐nitrophenol, among the best reported non‐noble metal catalysts. The greatly enhanced catalytic activity is attributed to the synergistic effects of abundant exposed catalytic edge sites, intimate P−N heterojunction between NiO and N, O‐MoS2, as well as the hollow porous structure. Moreover, the recovered N, O‐MoS2/NiO hollow microspheres can be reused in successive 8 cycles without much losing its activity. These results suggest that the novel N, O‐MoS2/NiO hollow microspheres had significant application potential for wastewater treatment.