The interaction between terbium-doped arginine functionalized hydroxyapatite nanoparticles (Arg@HAP^Tb NPs) and cells, and the hindered endocytosis mechanisms of human umbilical vein endothelial cells (HUVECs) were studied by observing the cell uptake of Arg@HAP^Tb NPs with laser scanning confocal microscopy. Average fluorescence intensity of cells after uptaking different concentrations of NPs was determined by flow cytometer. The results indicate that internalized Arg@HAP^Tb NPs mainly exist in the cytoplasm of HUVECs, and most of them distribute around the cell nuclei. The entrapment of Arg@HAP^Tb NPs shows time-dependent and concentration- dependent manners with optimal time of 4 h and concentration of 50 mg/L. Arginine modification significantly improves the uptake efficiency of HAP^Tb NPs. The entry of Arg@HAP^Tb NPs into HUVECs is mainly through concave protein-mediated endocytosis, an energy-dependent active transport process.