Abstract：Objective：To explore the molecular mechanism of Tanshinone ⅡA in inhibiting oxidized low-density lipoprotein （ox-LDL） induced proliferation of vascular smooth muscle cells and Warburg effect by regulating the PKM2/ EGFR signaling pathway. Methods： The human aortic smooth muscle cells were used as the research object. The negative control group，the ox-LDL control group and the low and high doses of Tanshinone ⅡA group（10、50 μg/mL） were respectively set up；MTT assay was used to detect the effect of Tanshinone ⅡA intervention on the proliferation of smooth muscle cells induced by ox-LDL， and flow cytometry was used to detect the changes in cell cycle； the changes in protein expression of pyruvate kinase isozyme type M2 （PKM2）， phosphorylated epidermal growth factor receptor （pEGFR），active β-catenin，cyclin D1，Glut1 and LDHA protein was detected by Western blotting， and the levels of PKM2 mRNA were detected by fluorescence quantitative PCR； glucose consumption and lactic acid production were measured by spectrophotometry. Results： Tanshinone ⅡA inhibited the ox-LDL-induced cell proliferation in a dose-dependent manner. The proportion of cells in G1 phase was elevated，and reduced in S phase and G2/M phase. Tanshinone ⅡA inhibited the expression of PKM2 by the regulation of proteins and transcriptional level， down-regulated the protein expression of pEGFR， active β-catenin， cyclin D1， Glut1 and LDHA， and reduced glucose uptake and lactic acid production. Conclusion：Tanshinone ⅡA can inhibit the ox-LDL-induced proliferation of smooth muscle cells and metabolic reprogramming by regulating PKM2-mediated EGFR.