Graphene quantum dot (GQD), a zero-dimensional material with size less than 10 nm, is a newly developed member of the graphene family. GQDs have become highly promising materials in various applications, including catalysis, bioimaging, energy conversion, and storage, owing to their unique physicochemical properties, such as excellent photoluminescence, biocompatibility, low toxicity, easy fabrication, and edge effect. Additionally, oxygen-containing functional groups such as −COOH, −COC-, −OH, −CHO, and −OCH3 play a crucial role in the structure of GQDs. Oxygen is located in different edges and the basal plane of GQDs. The unique architecture of oxygen inside the structure of GQDs and the outstanding properties and performance of GQDs provide a powerful impetus to use GQDs as a promising material with applicability in various fields. In this chapter, we describe the possible structure, application, and critical role of the oxygen-containing functional group on the essential properties and application of GQDs. Finally, we provide a brief outlook to point out the issues that need to settle for further development.