<p>The preparation of pyridine N-oxides plays a critical role in functionalization of pyridines, which enhances the physical, chemical and biological properties of pyridine derivatives. And, the corresponding N-oxides are usually generated easily from the oxidation of pyridines by peracids. However, the peracids are extremely explosive even though they are used via preparation in situ. In this context, we developed a highly safe, economical and practical strategy to produce pyridine N-oxides using the cheap and environmentally friend H₂O₂ as terminal oxidation in continuous flow system. The solid-supported polyacrylic acid was used as catalyst which improved the reaction stability and operational safety and was reusable. In addition, the mixing efficiency was also enhanced by the solid-supported catalyst and made the scale-up synthesis achievable. Specifically, the output of this continuous flow synthesis could be increased to 67.93&#xa0;kg/d and 24.8 t/a using a thicker tube reactor which was 200&#xa0;m long, 1&#xa0;cm thick and filled with solid-supported acid catalyst to give 10&#xa0;L volume.</p> Graphical abstract <p></p>