To the best of our knowledge, this is the first report to show that egr-1 is markedly induced in epithelial cells after exposure to silica and mainly through ERK1/2, P38 MAPK pathway, which suggests Egr-1 is an essential regulator in silicosis, and underlines a new molecular mechanism for fibrosis induced by silica. Here, MAPK3 is linked to silicosis.