The present report highlights our results on synthesis of NaYF4:Yb,Er@SiO2@Ag core–shell nanoparticles (CSNPs) for plasmon-enhanced upconversion luminescence (UCL). Hydrophilic surface UCL nanoparticles (UCLNPs) as cores were obtained by precipitation of Rare Earth Elements (REE) chlorides from water-alcohol solutions. The formation of a hydrophobic surface of α-NaYF4:Yb,Er NPs was achieved by thermolysis method at 280 °C and β-NaYF4:Yb,Er by precipitation method in nonpolar medium at 320 °C. Silica shell was formed by the modified Stöber method on the surfaces of UCLNPs with different polarity and phase composition. A mixture of hexane-cyclohexane-isopropyl alcohol was used as a medium for the formation of mononuclear CSNPs on hydrophobic surfaces of cores with different thicknesses of the silica shell: 5 nm and 14 nm. Formation of a predetermined thickness of silica shell was carried out by introducing a precise quantity of TEOS taking into account the size of core NPs with molar ratio TEOS: H2O equal to 1:6. The morphology and phase composition of cores and CSNPs were examined by transmission electron microscopy and selected area electron diffraction, respectively. The insertion of Ag NPs into the structure of NaYF4:Yb,Er@SiO2 was carried out in parallel at the stage of shell formation, which made this synthesis a one-step process. The control of the size of Ag NPs was implemented through the use of a colloidal solution of NPs of the cluster structure by changing the polarity of the medium. The highest intensity enhancement of 85-fold with 5 nm and 29-fold with 14 nm shell thickness was recorded, respectively. For the first time, tests on bioimaging of neutrophil cells by those CSNPs are demonstrated.