Collectively, we demonstrated that heme induces SIRS through the ROS/HMGB1/NLRP3 pathway-regulated endothelial cell pyroptosis in mice, and hemopexin, a heme scavenger, and glycyrrhizin, a HMGB1 inhibitor, may be the potential strategies for further study for SIRS following the RFA of hepatic hemangioma for the first time. Here, HPX is linked to Hepatic hemangioma.