Certain human Ether-à-go-go-Related Gene (hERG) blockers can facilitate hERG activation to increase hERG currents, which may reduce proarrhythmic potential. However, the molecular mechanism involved in the facilitation effect of hERG blockers remains unclear. Here, we demonstrate that 1) nifekalant accesses the receptor site within the pore of the open or inactivated channels at depolarized potentials, 2) upon return to the resting potentials, channels close and trap nifekalant inside, 3) trapped nifekalant biases the open-closed equilibrium towards the open state, and 4) the kinetics of drug escape from the channel are faster than channel closing rates at potentials where facilitation of hERG current is observed, thereby drug unbinding reveals channels that have been biased towards the open state. Simulations with a Markov model of such nifekalant-hERG interaction successfully reproduce key characteristics of hERG facilitation. We also present a potential structural model for hERG channel facilitation through drug interactions with the hydrophobic pocket of the hERG pore domain. This pattern of interaction is consistent with experimental data suggesting facilitating drugs may act as a wedge to bias hERG channel equilibrium towards the open state and increase hERG current amplitude in response to low-voltage depolarization.