In this study, we demonstrate that there is increased SIX1 transcript and protein expression, and increased transcript and protein expression of its cofactors EYA1 and EYA2, in IPF compared with controls; we also demonstrate that conditional deletion of Six1 and overexpression in AT2 cells in mice can significantly attenuate or exacerbate lung fibrosis, respectively. Here, SIX1 is linked to idiopathic pulmonary fibrosis.