In this work, taking graphitic carbon nitride (g-C3N4) as an example, the synergistic utilization of the advantages of two-dimensional (2D) structure and heteroatom modification is realized. To better understand the role of such structure tailoring, the complicated photocatalytic reaction involving multiple small molecules, namely NO removal, is selected to serve as a model reaction. The experimental results find that the 2D g-C3N4 with oxygen modification (2D OCN) exhibits enhanced performance with good stability in photocatalytic NO removal compared to pristine g-C3N4, as a result for the improved charge separation and optimized molecular adsorption. On one hand, the 2D structure of OCN can shorten the charge migration distance, endow the semiconductor improved redox ability and provide large specific area for reaction proceeding. On the other hand, the oxygen modification could optimize the adsorption ability of reaction molecules (NO and O-2) benefiting the surface catalytic reaction. All the merits mentioned above are supported by detailed characterization and theoretical calculation. This article presented here provides a case study for designing efficient photocatalyst and an approach to analyze the correlation between structure and performance.