In this study, we demonstrated that 1) hypoxia promotes normal and IPF human pulmonary fibroblast proliferation, 2) hypoxia promotes the G1/S phase transition, 3) hypoxia activates NFAT signaling via HIF-2α, and 4) NFATc2 is required for hypoxia-induced cell proliferation. Here, EPAS1 is linked to idiopathic pulmonary fibrosis.