The voltage-dependent cardiac sodium channel plays a key role in cardiac excitability and conduction and it is the drug target of medically important. However, its atomic- resolution structure is still lack. Here, we report a modeled structure of Nav1.5 pore domain in closed state. The structure was constructed by Rosetta-membrane homology modeling method based on the template of eukaryotic Navchannel NavPaS and selected by energy and direct coupling analysis (DCA). Moreover, this structure was optimized through molecular dynamical simulation in the lipid membrane bilayer. Finally, to validate the constructed model, the binding energy and binding sites of closed-state local anesthetics (LAs) in the modeled structure were computed by the MM-GBSA method and the results are in agreement with experiments. The modeled structure of Nav1.5 pore domain in closed state may be useful to explore molecular mechanism of a state-dependent drug binding and helpful for new drug development.