Objective To investigate the effect of fibroblast growth factor 23 (FGF23) on the growth, immune balance and epithelial-mesenchymal transition (EMT) of bronchial epithelial cells (16HBE). Methods 16HBE cells were transfected with NC-shRNA or FGF23-shRNA using Lipofectamine 3000 transfection reagent. After transfection, cells were treated with 10 ng/mL of transforming growth factor-β1 (TGF-β1) for 48 h. 16HBE cells were grouped as follows: Control group, NC-shRNA group, FGF23-shRNA group, TGF-β1 group, NC-shRNA+TGF-β1 group and FGF23-shRNA+TGF-β1 group. Cell proliferation was detected by CCK-8 method. The levels of interferon-γ (IFN-γ), interleukin (IL)-4, IL-17 and IL-10 in the supernatant of 16HBE cells were detected using ELISA kits. The mRNA or protein expressions of FGF23, Klotho, FGFR4, E-cadherin, α-SMA and N-cadherin in 16HBE cells were detected by qRT-PCR, Western blot or immunofluorescence staining.Results Compared with TGF-β1 group, the OD 450nm value of FGF23-shRNA+TGF-β1 group decreased by 34.75% (P<0.05). Compared with TGF-β1 group, the levels of IFN-γ and IL-10 in FGF23-shRNA+TGF-β1 group were increased, while the levels of IL-4 and IL-17 were decreased (P<0.05). Compared with TGF-β1 group, the expression level of E-cadherin protein in FGF23-shRNA+TGF-β1 group was increased, while α-SMA was decreased (P<0.05). Compared with TGF-β1 group, the relative fluorescence intensity of E-cadherin in FGF23-shRNA+TGF-β1 group was increased, while the N-cadherin was decreased (P<0.05). Compared with TGF-β1 group, the mRNA and protein expression levels of FGF23 and FGFR4 in FGF23-shRNA+TGF-β1 group were decreased, while Klotho was increased (P<0.05). Conclusion Down-regulation of FGF23 inhibits TGF-β1-induced growth and EMT of 16HBE cells, and corrects the imbalance of Th1/Th2 and Treg/Th17. FGF23-Klotho-FGFR4 signaling may be a molecular target for asthma therapy