Surface functionalized ZrO2 nanoparticles show strong photoluminescence and are a versatile tool for cellular targeting due to their chemical functionality. They are highly photostable, biocompatible and amenable to coupling with bioligands (e.g. secondary goat anti-rabbit antibody (GAR) and tri-phenyl phosphine (TPP)) via carbodiimide chemistry. Antibody (GAR) functionalized ZrO2 nanoparticles were used to image the nuclear protein Sirt6, whereas triphenyl phosphonium ion (TPP) functionalized ZrO2 nanoparticles specifically targeted the mitochondria. The versatility and easiness of the ZrO2 surface modification opens up new possibilities for designing non-toxic water dispersible and photostable photoluminescent NPs.