Hexagonal-phase NaYbF4:Er(3+) upconversion nanoparticles (UCNPs) have been synthesized via a co-precipitation method in high-boiling-point solvents, and remarkably enhanced upconversion luminescence, particularly in red emission bands (650-670 nm) in NaYbF4:Er(3+) UCNPs, has been achieved by Mn(2+) doping. The underlying reason for luminescence enhancement by Mn(2+) doping is explored by a series of controlled experiments, and a mechanism of enhancement based on the decrease of Na(+)-vacancies and organic adsorption is proposed. The Mn(2+) substitution disturbs the equilibrium of the charge and crystal lattice in the hexagonal-phase NaYbF4:Er(3+) UCNPs, which makes the Na(+)-vacancies that quenched luminescence become filled with Na(+) or Mn(2+) to offset the imbalance of the charge and electron cloud distortion. In addition, the Mn(2+) doping at the surface of UCNPs could reduce the organic adsorption on the surface of the UCNPs by an extra F(-) ion on the grain surface resulting in luminescence enhancement. Therefore, the Mn(2+)-doping approach provides a facile strategy for improvement of luminescence, which will impact on the field of bioimaging based on UCNP nanoprobes.