Abstract： Objective:To investigate the effect of interleukin-8 (IL-8) on the progression of oral squamous cell carcinoma (OSCC) by interfering with the expression of forkhead transcription factor P3 (FOXP3) in neutrophils.Methods:Thirty-six patients with OSCC and 12 healthy volunteers with normal oral mucosa were collected between December 2016 and December 2019. Immunohistochemical staining was used to detect the expression of FOXP3 and IL-8 in tissues; immunofluorescence assay was used to detect the expression of FOXP3 in neutrophils of cancer tissues. Human tongue squamous cell carcinoma SCC-9 cell line was purchased, and neutrophils were extracted from peripheral blood of healthy volunteers to analyze the effects of neutrophils and IL-8 on the proliferation of SCC-9 cells. RT-qPCR was used to detect the effect of IL-8 on FOXP3 mRNA expression in neutrophils. After being down-regulated by P60, the effect of FOXP3 expression in neutrophils on proliferation and migration of SCC-9 cells was analyzed.Results:The positive expression rates of FOXP3 and IL-8 in OSCC tissues (71.05%, 76.32%) were significantly higher than those in adjacent normal oral mucosa tissues (8.70%, 4.35%) ( P<0.05) . The expression of FOXP3 protein in the neutrophils in OSCC tissues was low, and its level decreased with the progression of the disease ( P<0.05) . The cell proliferation rate of the SCC-9+ neutrophil+ IL-8 group was significantly higher than those of the SCC-9 group, SCC-9+ neutrophil group and SCC-9+ IL-8 group ( P<0.05) . The FOXP3 mRNA level of neutrophils in the IL-8 intervention group was lower than that in the PBS control group ( P<0.05) . The proliferation rate of SCC-9+ neutrophils+ P60 group was significantly higher than those of SCC-9 group, SCC-9+ neutrophils group and SCC-9+ P60 group ( P<0.05) . After 24 hours of incubation, the wound healing rate of SCC-9+ neutrophils+ P60 group was significantly higher than those of SCC-9 group, SCC-9+ neutrophils group and SCC-9+ P60 group ( P<0.05) . Conclusion:FOXP3 and IL-8 are highly expressed in OSCC tissue, while Foxp3 is lowly expressed in neutrophils, indicating that IL-8 may promote SCC-9 cell proliferation and migration by down-regulating FOXP3 gene expression and chemotaxis of neutrophils into tumor microenvironment.