Compared with fresh batteries, the safety research of lithium-ion batteries in the whole life cycle is more worthy of attention. The large-size prismatic aluminum-shell lithium iron phosphate power batteries in two states, i.e., beginning of life (BOL) and end of life (EOL) were selected as the research objects. The specific heat capacity, thermal conductivity, material's thermal stability and direct current internal resistance of BOL and EOL batteries were analyzed firstly. The safety differences of BOL and EOL batteries were compared in detail, such as over-discharge, over-charge, external short-circuit, heating, nail penetration, and crush, etc. The results show that compared to BOL battery, the specific heat capacity of the EOL battery decreases from 1.088 J/(g·℃) to 1.065 J/(g·℃). The thermal conductivity in the height, width, and thickness directions of the battery decreased from 25.84, 21.21, 1.05 W/(m·K) to 22.20, 18.44, 1.00 W/(m·K). The exothermic peaks shifted to low temperature, and the exothermic peak of solid electrolyte interface film decomposition appeared near 121℃, and the exothermic enthalpy of the reaction between the intercalated lithium-graphite compounds, electrolyte, and binder decreased from 1019 J/g to 841 J/g. In terms of safety, the EOL battery after over-discharge generated more gas, leading to a larger thickness swelling. Over-charge produced more gas with EOL battery, and the vent opened ahead of 7% state of charge. The external short-circuit current cannot fuse the connecting structure, and the battery would discharge continually to over-discharge state, giving more gas production and serious swelling. The nail penetration did not release smoke, the vent was not broke, and the safety was greatly improved. The temperature of thermal runaway caused by heating was close, and the differences of other safety test items were little. The research results enriched the research on the safety performance of lithium-ion batteries in the whole life cycle, and contributed to the thermal runaway protection design of batteries, modules and systems.