A large number of studies showed that cancer stromal cells, such as inflammatory cells, endothelial cells and fibroblasts, induced resistance to chemotherapy in lung cancer.25 In the stromal cells, fibroblasts have been reported to be a main player in this phenomenon.4, 26 In the present study, we revealed that PAI‐1 inhibition limited the chemotherapy resistance through suppressing the MF characteristics of CAFs. The gene discussed is SERPINE1; the disease is lung cancer.