Objective: To investigate the protective effect and mechanism of fibroblast growth factor 1 (FGF1) on transforming growth factor β1 (TGF-β1)-induced activation of human renal fibroblasts. Methods: NRK-49F cells were over-expressed with FGF1 and then stimulated with 2 ng/mL TGF-β1 to induce renal fibrosis model. Cell density and BrdU positive rate were observed after 24 h. The cell viability was determined by MTT assay. The expressions of α-SMA and FN protein in NRK-49F cells were detected by immunofluorescence and Western blot. The changes of p-S6, p-Akt (Ser473), β-catenin and p-Smad3 (Ser423/425) in NRK-49F cells were detected by immunofluorescence and Western blot. Results: Exogenous TGF-β1 promoted the proliferation of renal fibroblasts in vitro, while over-expression of FGF1 reduced TGF-β1-induced renal fibroblast proliferation and reduced renal fibroblast activation stimulated by TGF-β1. Over-expression of FGF1 inhibited TGF-β1-induced Akt/β-catenin alteration, but did not inhibit Smad signaling. Conclusion: The protective effect of FGF1 on TGF-β1-induced activation of human renal fibroblasts may be achieved through the Akt/ β-catenin pathway.