Internal short-circuit is the most dangerous abusive condition for Li-ion batteries and has been the root cause for several catastrophic accidents involving Li-ion batteries in recent years. Large-format Li-ion batteries are particularly vulnerable to internal short-circuits because of high energy content. Nail penetration test is commonly used to study the internal short-circuits, but the test results usually have poor reproducibility and offer limited insight. In this work, a 3 D multiscale electrochemical-thermal coupled model is used to investigate the nail penetration process in a large-format Li-ion cell. A parametric study is carried out and the results reveal strong coupling of the cell thermal response and electrochemical behaviour, which is influenced substantially by key parameters including shorting resistance, nail diameter, nail thermal conductivity, and cell capacity. The present study provides some insight that will help design more reliable experimental internal short-circuit testing protocols and improve the abuse tolerance of Li-ion cells.