In the present work, mono-disperse and uniform orthorhombic lutetium fluoride (LuF3) nanocrystals with an average size of about 35 nm have been successfully synthesized by a simple ionothermal method without any template. The infrared (IR) to visible up-conversion (UC) photoluminescence of LuF3 doped with Yb3+, Tm3+, and Ho3+ under 980 nm excitation was systemically studied. The intensity of near infrared (NIR) to visible up-conversion emission of Tm3+ was improved efficiently by adding Yb3+ and Ho3+ in LuF3, especially for the broad NIR emission band located at 812 nm. Meanwhile, compared to the Yb3+ and Tm3+ co-doped LuF3, the ratio of red to green emission in the Yb3+, TmS+, and HoS+ co-doped LuF3 changed greatly, and a bright yellowish-green emission was observed under 980 nm laser excitation. It shows that Yb3+, Tm3+ and Ho3+ co-doped LuF3 nanocrystals provided a potential application in vitro and in vivo bio-imaging, color displays and optical storage.