In our work, the orthorhombic K2YF5 nanocrystals were successfully synthesized via solvothermal method in a mixture of oleic acid and 1-Hexanol. The up-conversion (UC) luminescent properties of orthorhombic K2YF5:Yb3+, Er3+/Tm3+ nanoparticles (NPs) were studied, and the multicolor output, including green, yellow-green, yellow, pink, and blue, was achieved by adjusting the concentrations of Yb3+ sensitizer ion and kinds of activator ions. Meanwhile, the optimal doping concentrations of Yb3+, Er3+/Tm3+ which is a condition that green or blue emissions intensity can reach a maximum were found under 980 nm laser diode (LD) excitation. Furthermore, the fluorescence lifetimes of S-4(3/2) excited state of Er3+ and (1)G(4) excited state of Tm3+ in the K2YF5:Yb3+, Er3+/Tm3+ were tested, which showed that the fluorescence lifetime can reach 1.14 ms and 0.57 ms at the optimal doping concentrations of Yb3+/Er3+ (30%/3%) and Yb3+/Tm3+ (25%/0.2%) respectively, indicating that the K2YF5 nanomaterial owns extremely strong UC emission intensity and long fluorescence lifetime. Indubitably, the outstanding optical properties will make K2YF5 NPs have potential applications in the fields of 3D displays, optical communications, phosphors, and so on.