Objective: To investigate the effect of demethylase obesity-associated protein(FTO) on the expression of tumor necrosis factor-α-stimulating gene-6(TSG-6) mRNA demethylation in keloid tissue and its role in scar formation. Methods: Fresh keloid tissue(experimental group) and normal skin tissue(control group) were randomlyselected, and the expression level of TSG-6 in the experimental group and control group was detected by immunofluorescence method. A probe expressing TSG-6 mRNA sense and antisense chain were constructed for RNA pulldown, followed by Western blot detection of samples in each group with N6-methyladenine(m6A) antibody. Real-time fluorescence quantitative polynucleotide chain reaction(qPCR) and Western blot were used to detect the expression of TSG-6 mRNA demethylase and methylase in the experimental group and control group. The expression levels of FTO in experimental group and control group were detected by immunofluorescence assay. Results: Immunofluorescence results showed that the expression level of TSG-6 in the experimental group was lower than that in the control group(P<0.01). Pulldown test results of biotin-labeled TSG-6 RNA showed that the m6A expression level of TSG-6 mRNA in the experimental group was lower than that in the control group(P<0.01). The results of qPCR showed that the expression level of FTO mRNA in the experimental group was higher than that in the control group(P<0.01). Western blot analysis showed that FTO protein expression in the experimental group was higher than that in the control group(P<0.001). Immunofluorescence results showed that the expression level of FTO in experimental group was higher than that in control group(P<0.001). Conclusion The demethylase FTO catalyzes the demethylation of TSG-6 mRNA and promotes the formation of keloid, which may provide a new idea and direction for clinical treatment of keloid.