The present study demonstrated that BrS-hiPSC-CMs with SCN10A and SCN5A variant displayed higher sensitivity to fever and inflammation challenge; PKA signaling mediated the effect of fever and ROS/IL-6 mediated the effect of inflammation on the phenotype of BrS-hiPSC-CMs; BrS-hiPSC-CMs with CACNB2 variant displayed higher sensitivity to inflammation challenge but not fever; the gene mutation may impact effects of fever and inflammatory factors on BrS-phenotype. This evidence concerns the gene IL6 and Fever.