To stabilize 5 V spinel LiNi0.5Mn1.5O4 (LNMO) cathode in organic electrolyte, electrochemically inactive and oxidation resistant polyvinylidene fluoride (PVDF) is applied onto the particle surface through a liquid coating process. The morphology, crystalline structure, and coating thickness of the as-prepared samples are analyzed with X-ray powder diffraction, Raman spectroscopy, and scanning and transmission electron microscopies. With the protection of PVDF wrapping layer, electrolyte decomposition at the electrode/electrolyte interface is greatly reduced and the growth of the solid electrolyte interface (SEI) on the cathode is effectively suppressed. Moreover, Mn dissolution into the electrolyte during long-term cycling is significantly decreased. As the result, the 5 V spinel LNMO cathode is effectively stabilized in organic electrolyte and its overall electrochemical performances are greatly enhanced. With 50 nm PVDF-wrapping, the LNMO composite cathode exhibits a capacity retention of 97.8% and 86.1% after 300 cycles at room and high temperature, respectively. The fatal impedance rise of the electrode during prolonged electrochemical cycles due to the surface evolution is also effectively suppressed.