Sc-based nanomaterials have attracted considerable attention due to their unique optical properties different from those of Ln/Y-based nanomaterials. However, studies on Sc-based nanomaterials are far from comprehensive. Particularly, nanoscale alkaline (Ca, Sr and Ba) scandium fluorides were almost ignored for their stringent synthetic conditions. Herein, we synthesize high-quality tetragonal phase Ba3Sc2F12 nanocrystals with uniform morphology and good dispersibility by carefully tailoring the reaction conditions, such as the molar ratio of reactants, temperature and reaction time. Then, the upconversion (UC) luminescence property of Ba3Sc2F12:Yb/Er (Ho) samples is investigated in detail. The doping concentrations of sensitizer (Yb3+) and activator (Er3+ and Ho3+) are optimized for the strongest UC luminescence, of which the corresponding energy transfer processes are also discussed. Moreover, tetragonal Ba3Sc2F12 nanocrystals can gradually transform into hexagonal Ba4Yb3F17 nanocrystals with the increase in Yb3+ doping content. This work provides a novel type of Sc-based nanomaterials with strong red UC emissions which are promising in high-resolution 3-dimensional color displays, laser, bioimaging and biolabels.