Objective To explore the role of sulforaphane (SFN) on the regulation of airway mucin 5AC mucin expression in the airway epithelial cell line (A549), and the underlying mechanism. Methods The experiments were performed in culture of PMA and H2O2 induced A549 in vitro. A549 cells divided into three groups: the control group, the model group (PMA and H2O2) and the intervention groups (SFN+PMA; SFN+H2O2). The intervention group's cells were pretreated with SFN for 30 mins before exposure to stimuli (PMA or H2O2). The MUC5AC, Nrf2 and the antioxidant gene HO-1, NQO1, GCLC mRNA levels were analyzed by real time-PCR, and protein production was assayed by western blot. Results Compared with the control group, expression of MUC5AC mucin was increased after being stimulated by PMA or H2O2 (P<0.05), but it was significantly inhibited by SFN (P<0.05). SFN induced the expression of Nrf2 gene and the antioxidant gene HO-1 (compared with the control and model groups,P<0.05). Conclusion Sulforaphane involves the airway mucous hypersecretion induced by PMA and H2O2, and Nrf2/HO-1 signaling pathway may play an important role in mucin MUC5AC regulation.