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. This evidence concerns the gene HMGB1 and liver hemangioma.