Recently, metal–organic frameworks (MOFs) have been extensively investigated as fluorescence chemsensors due to their tunable porosity, framework structure and photoluminescence properties. In this paper, a well-known Zr(IV)-based MOF, UiO-66-NH₂ was demonstrated to have capability for detection of L-lysine (Lys) and L-arginine (Arg) selectively from common essential amino acids in aqueous media via a fluorescence turn-on mechanism. Further investigation reveals its high sensitivity and strong anti-interference properties. Moreover, the possible mechanism for sensing Lys and Arg was explored by FT-IR and ¹H-NMR, and the results indicate that the enhancement of the fluorescence could be ascribed to the adsorption of Lys/Arg and the hydrogen bonding interactions between Lys/Arg and the amino group of UiO-66-NH₂. The difference of the sensing capacity and sensitivity between UiO-66 and UiO-66-NH₂ revealed that the amino group plays an essential role in the sensing performance. This work presents a unique example of the functional group dependent sensing properties of MOFs.