Thermal stability of LiPF6-based electrolyte (1M LiPF6/EC+DMC) was studied by in-situ FTIR spectroscopy and C80 calorimetry, which indicated that the electrolyte underwent furious polymerization and decomposition reactions and sharp heat flow was generated below 225°C. The thermal stability of the electrolyte in contact with various delithiated cathodes (Li x CoO2, Li x Ni0.8Co0.15Al0.05O2, Li x Ni1/3Co1/3Mn1/3O2, Li x Mn2O4, Li x Ni0.5Mn0.5O2, Li x Ni0.5Mn1.5O4 and Li x FePO4) was also investigated by C80 calorimetry. The results show that the cathode materials except for Li x FePO4 usually have an enhancement effect on the decomposition of the electrolyte, but Li x FePO4 exhibits a suppression effect on the reactions of the electrolyte. Li x FePO4 is found to be with excellent thermal stability. Among the other cathodes, Li x CoO2, Li x Ni0.8Co0.15Al0.05O2, Li x Ni0.5Mn0.5O2 and Li x Ni0.5Mn1.5O4 promote the decomposition of electrolyte by releasing oxygen and thus considered not favorable for safety, but Li x Ni1/3Co1/3Mn1/3O2 with a lesser reaction heat and Li x Mn2O4 with even less heat flow in the low temperature range (50–225°C) are believed as promising cathodes for better safety. By comparing X-ray diffraction (XRD) patterns of these cathode materials at room temperature and those heated to 300°C in the presence of the electrolyte, we have found that Li x FePO4 only has experienced tiny structure change, which is greatly different from the other cathode materials.