The main concern hindering the large-scale application of lithium-ion batteries (LIBs) in electric vehicles (EV) is thermal runaway (TR). In this work, three-dimensional (3D) TR and conjugate heat transfer modeling of a LIB pack consisting of 12 prismatic cells is performed. Three strategies of thermal spread protection are investigated by numerical simulation. Inserting insulation layers with different thermal conductivities between adjacent LIBs, it is observed that the time to trigger TR in cell 2 delays by 23 s, 31 s, 51 s, and 132 s. When the insulation layer material is 2 mm and 3 mm aerogel, cell 2 produces TR time of 312 s and 944 s. It has reached the standard of safety, and adjacent LIBs could not generate in TR for at least 300 s. The study also shows cell 2 causing TR at 56 s, 51 s, 48 s, and 46 s with cold plates by different mainstream velocities. To completely block the propagation of TR, this study proposes a novel hybrid protective strategy based on insulation layers and cold plates. As a result, the average temperature of cell 2 does not reach more than 80°C, LIB pack tends to be in thermal equilibrium to prevent safety accidents from occurring. The modeling approach used in this study is demonstrated to be an effective tool for the thermal protection design of power system in EV.