Our study, for the first time, confirms that liquiritigenin can alleviate bleomycin-induced pulmonary fibrosis in mice and provides in vitro evidence that liquiritigenin could inhibit TGF-β-induced fibroblasts to myofibroblasts differentiation, the effect may be mediated by the SIRT1/Nrf2 signaling pathway. The gene discussed is TGFB1; the disease is pulmonary fibrosis.