Lithium-ion batteries (LIBs) have been dominating the consumer, power and energy storage battery market for the past three decades, while the never-ending pursuit to the energy density, rate capability and service condition pushes operating LIBs in an even greater risk state. Herein, a safety design strategy is developed in practical graphite- LiNi0.6Co0.1Mn0.3O2 (NCM613) lithium-ion pouch cells by integrating a multi-functional separator. The internal short circuit triggered by lithium plating of the anode can be accurately and quickly warned in advance, taking advantage of the in-plane electron conductivity of the separator. On the other hand, the joint improvement in thermal stability and thermal conductivity of the separator enhances the resistance of the battery to thermal runaway. Benefiting from the superior wettability and lower direct current resistance, the pouch cells integrated with multi-functional separators exhibit ignorable or acceptable deterioration on the electrochemical properties, including internal resistance, charge/discharge rate, high-low temperature capacity, cyclability, and high-temperature storage performance. The safety design strategy endows the inherently unsafe LIBs with double insurance of warning and resisting to thermal runaway.