In order to study the optimal hydrothermal process conditions of nano-phosphor YPO4:2%Sm3+, using the fluorescence intensity as an indicator, the hydrothermal process conditions (reaction temperature, reaction time, the ratio of anion to cation in the solution and pH value) of the nano-phosphor YPO4:2%Sm3+ were optimized by L9(34) orthogonal experiment. Then, the composition, structure, morphology and luminescent property of the sample were characterized and analyzed by X-ray diffractometry (XRD), scanning electron microscopy (SEM and EDS), infrared spectrometer (FT-IR), ultraviolet spectrometer (UV) and fluorescence spectrophotometer (FL). The experimental results showed that the primary and secondary factors affecting the hydrothermal process conditions of nano-phosphor YPO4:2%Sm3+ were reaction temperature>pH value>reaction time>the ratio of anion to cation. The optimal hydrothermal process conditions of nano-phosphor YPO4:2%Sm3+ were reaction temperature of 200℃, pH=3, reaction time of 12 h, the ratio of anion to cation of 3:1. The optimum nano-phosphors was a single tetragonal crystal with the morphology of nanospheres, the maximum fluorescence intensity, and fluorescence life time of 0.1719 ms, band gap of 5.14 eV, color coordinate of X=0.5563, Y=0.4339.