Solvent plays a vital role in the syntheses, purifications, and broad applications of upconversion nanoparticles (UCNPs). In this work, the effect of various dispersive solvents, including single solvents and mixed solvents, on the luminescence properties of NaYF4:Yb3+, Er3+ UCNPs was studied systematically. The differences in both upconversion luminescence (UCL) intensities and color outputs of the nanoparticles were observed when dispersing the UCNPs in deuterium oxide, dimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethanol, or water. The attenuation of the excitation and emission light of the UCNPs caused by absorption of the solvents, as well as the high-frequency vibrational groups of the solvents, such as -OH, -CH2, and -CH3 groups, are responsible for the decrease in UCL intensities and increase in the red to green emission intensity ratios (RGR). The changes in water or OH- ion contents of ethanol/water mixed solvent triggered similar changes in UCL properties. Interestingly, the quenching of the solvents for the UCL cannot be fully eliminated by changing the dispersive solvents once the UCNPs have touched the solvents containing high-frequency vibrational groups. Our work will facilitate the comprehension of the solvent induced luminescence variations of the nanoparticles and provide guidance for their applications.