In this study, N-doped few-layer MoS2 piezocatalysts were successfully prepared by a one-pot hydrothermal method with urea as a nitrogen source. Benefiting from the optimized proportion of minority layers at edge positions and higher conductivity by N doping, the optimal N-doped few-layer MoS2 (120 mg of added urea) sample showed the optimal piezocatalytic activity for Rhodamine B (RhB) and levofloxacin (LEV), reaching 84.6 and 73.1% with the reaction kinetic rate constant of 0.020 86 and 0.017 05 min-1, respectively. In addition, the generation of superoxide radicals (·O2-) from the 120-MoS2 sample was determined to be greater than that from the 0-MoS2 sample in the piezocatalyst process by free radical scavenging experiments and electron paramagnetic resonance tests. Based on experimental data, a potential mechanism has been proposed to explain the enhanced piezocatalyst performance of N-doped few-layer MoS2. This research sheds new light on the development of efficient, cost-effective MoS2 piezoelectric catalysts through the doping of non-metallic dopants.