Objective To detect the expression of growth factor independence 1 (GFI-1) in peripheral blood of patients with Sézary syndrome and normal persons, so as to provide a theoretical basis for developing GFI-1 gene target therapy. Methods CD4⁺CD7^- Sézary cells (SS cells) were separated and purified from peripheral blood of 7 patients with Sézary syndrome by flow cytometry, CD4⁺T cells from peripheral blood of 10 normal persons, Sézary syndrome-derived cell line Hut78 and human acute T cell leukemia cell line Jurkat as controls. The mRNA and protein expressions of GFI-1 were detected by qPCR and Western blotting, respectively. Then after interferon-α-2b (IFN-α2b) was used to induce Hut78 cell apoptosis, the cell proliferation was measured by MTS, the mRNA expression of GFI-1, cell cycle-dependent protein kinase inhibitor P21, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and Caspase-3 was detected by qPCR, and the cell apoptosis was detected by flow cytometry. Results The expression of GFI-1 mRNA in the SS cells was significantly higher than that in the Jurkat and CD4⁺T cells (all P<0.05). The expression of GFI-1 protein in the SS cells and Hut78 cells was significantly higher than that in the Jurkat and CD4⁺T cells (all P<0.05). IFN-α2b significantly inhibited the proliferation of Hut78 cells, and the effect was concentration-dependent and time-dependent. The mRNA expression of GFI-1 in Hut78 cells was significantly decreased in a time-dependent manner at 12 h and 24 h treated with IFN-α2b, while the mRNA expressions of P21, TRAIL and Caspase-3 were significantly increased (P<0.05). The apoptosis of Hut78 cells was significantly increased at 12 h and 24 h treated with IFN-α2b (P<0.05). Conclusion The expression of GFI-1 gene in peripheral blood SS cells of patients with Sézary syndrome is increased and can be inhibited by IFN-α2b, indicating that GFI-1 gene may play an important regulatory role in tumor proliferation of SS cells in patients with Sézary syndrome.