An efficient method for labeling individual proteins in live cells is required for investigations into biological mechanisms and cellular processes. Here we describe the preparation of small quantum dots (QDs) that target membrane surface proteins bearing a hexahistidine-tag (His(6)-tag) via specific binding to an nitrilotriacetic acid complex of nickel(II) (NTA center dot Ni2+) on the QD surfaces. We showed that the NTA center dot Ni2+-QDs bound to His-tag functionalized beads as a cellular mimic with high specificity and that QDs successfully targeted His(6)-tagged vesicle-associated membrane proteins (VMAP) on cell surfaces. This strategy provides an efficient approach to monitoring synaptic protein dynamics in spatially restricted and confined biological environments.