Graphene oxide (GO) is widely used in biosensors and bioimaging because of its high quenching efficiency, facile chemical conjugation, unique amphiphile property, and low cost for preparation. However, the nanometer size effect of GO on GO-DNA interaction has long been ignored and remains unknown. Here we examined the nanometer size effect of GO on GO-DNA interactions. We concluded that GO of ∼200 nm (lateral nanometer size) possessed the highest fluorescence quenching efficiency whereas GO of ∼40 nm demonstrated much weaker ability to quench the fluorescence. We employed the nanometer size effect of GO to program the dynamic ranges and sensitivity of mercury sensors. Three dynamic ranges (1 to 40 nM, 1 to 15 nM, and 0.1 to 5 nM) were obtained with this size modulation. The sensitivity (slope of titration curve) was programmed from 15.3 ± 1.27 nM(-1) to 106.2 ± 3.96 nM(-1).