We demonstrated that HMGB1 increased Drp1 phosphorylation and Drp1‐dependent mitochondrial fission through activation of ERK1/2 signalling pathway, and subsequently stimulated autophagy activation, which further led to BMPR2 lysosomal degradation and Id1 downregulation, and ultimately promoted PASMCs proliferation/migration and pulmonary vascular remodelling in PAH. Here, HMGB1 is linked to pulmonary arterial hypertension.