Synthesis of two-dimensional (2D) CdSe with microscale lateral dimensions is a challenge in colloidal chemistry. Herein, micrometer-sized CdSe nanosheets (NSs) have been successfully synthesized through a versatile cation exchange approach using microscale Cu2-xSe NSs as a template. By replacing Cu+ ion with Cd2+ ion within the NSs template, CdSe NSs with lateral dimensions up to 6 mu m, beyond which can be synthesized directly by colloidal chemistry, have been obtained. Notably, resulting CdSe NSs retain the 2D morphology with well-defined shape and size. We then demonstrate the use of large CdSe NSs in the application of local photocatalytic H-2 generation. The H-2 gas bubble evolution on the individual NSs was successfully detected and the local rate was determined.