Abstract: OBJECTIVE To study the effect of isoliquiritigenin on cell proliferation， apoptosis induction， mRNA expression of endoplasmic reticulum stress related gene ATF4， DDIT3 and TNFRSF10B in NCI-H157 human lung cancer cell line. METHODS NCI-H157 cells were cultured and treated with various concentrations isoliquiritigenin. The cell proliferation was analyzed by MTT and the occurrence of cell apoptosis was examined by flow cytometry. ATF4， DDIT3 and TNFRSF10B gene mRNA expression were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS Isoliquiritigenin significantly inhibited NCI-H157 cell proliferation in a dose and time dependent manner. The results of flow cytometry revealed that isoliquiritigenin could induce apoptosis in NCI-H157 cells. Real-time quantitative RT-PCR showed that isoliquiritigenin up-regulated mRNA expression of ATF4， DDIT3 and TNFRSF10B（P<0.05~0.01）. CONCLUSION Isoliquiritigenin can inhibit NCI-H157 cell proliferation， induce cell apoptosis by activating the endoplasmic reticulum stress response.