We propose a novel and efficient F- anion doping strategy for enhancing upconversion luminescence in upconversion nanophosphors. NaGd(MoO4)2:Yb3+/Er3+ nanophosphors doped with different F- contents are synthesized hydrothermally. Rietveld refinement results obtained from X-ray diffraction data indicate that the Gd-O bond length decreases and the O-Gd-O bond angle varies with increasing F- content, resulting in augmented local crystal field strength and distorted local site symmetry of the dopant lanthanide sites. Judd-Ofelt analysis suggests that the calculated radiative quantum efficiency of the 4S3/2 level and the radiative branching ratio of 4S3/2 → 4I15/2 transition in F--doped NaGd(MoO4)2:Yb3+/Er3+ nanophosphors are much greater than those in F- anion-free samples. It is inferred that F- anion doping helps to reduce the nonradiative transition probabilities based on the luminescence dynamics. Rietveld refinement results and Judd-Ofelt analysis confirm jointly that doping of interstitial F- anions could enhance local crystal field strength with odd parity and modify site symmetry of the lanthanide activator ions, leading to enhanced radiative transitions and inhibited nonradiative transitions. A maximum of 17-fold enhancement of total emission intensity is found in NaGd(MoO4)2:Yb3+/Er3+/F- nanophosphors compared with F- anion-free counterparts. The proposed F- anion doping strategy provides an alternative approach for enhancing upconversion luminescence efficiency and could be extended to other inorganic upconversion nanomaterials.