OBJECTIVE: To investigate the effects of hydrogen water on proliferation, differentiation, collagen secretion and Nrf2 expression in paraquat-induced human lung fibroblasts. METHODS: In vitro cultured human lung fibroblasts (HFL1) exposed to 600 μmol/L paraquat (PQ) for 24 h were treated with hydrogen water with or without RNA interference of Nrf2 expression. The changes in the cell proliferation were examined using MTT assay, and the expressions of Col-I, Col-III, α-SMA and Nrf2 in the cells were detected using Western blotting, real-time quantitative PCR and immunofluorescence assay. The contents of SOD, CAT and GSH in the cells were determined with ELISA. RESULTS: Compared with the PQ-exposed cells, the cells with hydrogen water treatment showed significantly lowered expressions of Col-I, Col-III, and α-SMA. Interference of Nrf2 expression obviously attenuated the effect of hydrogen water on PQ-exposed cells. Hydrogen water treatment significantly increased the expression of Nrf2 and promoted the production of the antioxidants in PQ-exposed lung fibroblasts. CONCLUSIONS: Hydrogen water enhances Nrf2 expression to promote the proliferation and production of antioxidants and inhibit the differentiation and collagen secretion in PQ-exposed human lung fibroblasts in vitro.