The safety is one of the persisting concerns related with Lithium-ion (Li-ion) batteries, among which the internal short-circuit is the most dangerous abusive situation and has always been the root cause for several catastrophic accidents in recent years. In this work, a 3D-layered electrochemical-thermal coupled model is employed to investigate the nail-penetration process in a Li-ion cell. The model is based on multilayer construction of a cell, and an effective strategy to evaluate the short-circuit area equivalent resistance (i.e. the equivalent resistance of short-circuit area that is caused by nail-penetration) during the penetration process is proposed. The developed model is proved to have capability of estimating the thermal runaway time, as well as the temperature distribution during nail-penetration process. It is also found that the active material loss during the nail-penetration process can be reconstructed by utilizing the developed model, which could provide understandings about the side reactions inside the cell during the nail-penetration process. The present study provides some insights about the nail-penetration process, and can be treated as a useful tool that helps the design of Li-ion cells for improving safety.