Rare-earth (Er3+, Ho3+, and Tm3+) doped yttrium oxide upconversion nanophosphors were synthesized using a single-step gas-phase flame synthesis method. The phosphors were characterized by X-ray diffractometry, transmission electron microscopy and fluorescence spectroscopy. The dependence of multi-photon emissions on excitation power was examined. The results show that particle size, morphology and photoluminescence intensity are strongly affected by flame temperature. The as-prepared nanophosphors are mostly single crystallites with an average size less than 30 nm. Under 980 nm laser diode excitation, bright blue, green and red emissions are visible from these phosphors which show potential applications in biological imaging and photodynamic therapy.