Hollow nanoparticles of hexagonal close-packed (hcp)-NaYF4:Yb,Er were synthesized by thermal decomposition of trifluoroacetate precursors at 340 °C via vacancy diffusion, likely due to the Kirkendall effect and Ostwald ripening mechanism. The average outer diameter, inner diameter, and shell thickness of these hollow particles were 14 ± 3 nm, 7 ± 2 nm, and 4 ± 1 nm, respectively. The surface effects on the fluorescence properties of these hollow particles were studied by comparing with that of solid NaYF4:Yb,Er (average size ∼15 ± 3 nm) and solid NaYF4 core/NaYF4:Yb,Er shell (NaYF4 core ∼10 ± 1 nm and NaYF4:Yb,Er shell ∼3 ± 2 nm) nanoparticles containing similar composition of Yb and Er ions. The green, red, and total emission intensities decreased with increasing upconversion active volume-normalized surface area. Surface coatings of undoped NaYF4 on both inner and outer surfaces of the hollow nanoparticles enhanced the total emission intensity by ∼19 and ∼5 times compared with those of the hollow and solid NaYF4:Yb,Er nanoparticles, respectively.