Epithelial–mesenchymal transition (EMT) is an important part of pulmonary fibrosis. Our earlier study illustrated that the acid sphingomyelinase (ASMase) pathway plays significant role in silica (SiO2)-induced transformation of lung fibroblasts into myofibroblasts. The metabolite of ASMase, ceramide (Cer), activates the inflammatory response by activating Nod-like receptor protein 3 (NLRP3) in macrophages, and NLRP3 is also involved in the EMT process. However, whether ASMase and NLRP3 are involved in regulating SiO2-induced EMT has not been confirmed. In this study, an in vitro model of EMT in human bronchial epithelial (HBE) cells was established by SiO2 dust staining to investigate the role of ASMase and NLRP3 in EMT and to provide new clues for the molecular mechanism of silicosis. HBE cells were stained with 100 μg/ml SiO2 dust for 72 h to establish the EMT model. The ASMase inhibitor desipramine decreased the level of S1P and the expression of α-smooth muscle actin (α-SMA) and NLRP3 in SiO2 dust-stained HBE cells, whereas the expression of E-cadherin (E-cad) increased. The NLRP3 inhibitor MCC950 inhibited the secretion of interleukin-1β (IL-1β) and decreased the expression of NLRP3, Caspase-1, and α-SMA in SiO2 dust-stained HBE cells, whereas E-cad expression increased and ASMase activity and S1P levels decreased. It was concluded that SiO2 dust increases the release of the inflammatory factor and induces EMT in HBE cells. Inhibition of ASMase activity or NLRP3 expression reduced the SiO2 dust-induced cell inflammatory response and slowed the occurrence of EMT in HBE cells. Therefore, NLRP3 and ASMase may interact in SiO2 dust-induced EMT in HBE cells.