Objective To investigate the interaction between staphylococcal nuclease domain containing protein 1 (SND1)and tissue differentiation-inducing non-coding RNA (TINCR), and the effect of SND1 on TINCR expression level and keloid growth. Methods Keloid tissue samples (n=27) were collected from patients with Ⅱ- or Ⅲ-degree burns who received treatment in Shaanxi Provincial People's Hospital from June 2016 to May 2018. Bioinformatics methods were used to predict RNA methylation sites in TINCR sequences; human primary normal skin fibroblasts (HFs) and keloid fibroblasts (KFs) were cultured and divided into HFs group and KFs group. KFs in logarithmic growth phase were taken, and divided into: (1) control group, empty vector group and methyltransferase-like protein 3 (METTL3) overexpression group, (2) control group and 3-deazaadenosine (DAA) group, and(3) control group, SND1 recombinant proteome group and SND1 proteome+DAA group. The relative expression level of TINCR in HFs and KFs was determined by real-time quantitative PCR (RT-qPCR); methylated RNA immunoprecipitation (MeRIP) followed by RT-qPCR was performed to analyze the methylation levels of TINCR; Western blotting was used to detect the relative expression levels of SND1 and METTL3 protein; the half-life of TINCR was determined by actinomycin D treatment combined with RT-qPCR,and the cell proliferation capacity was assessed with CCK-8 and clone assays. A keloid xenograft model was generated with 18 BALB/c nude mice, and then randomly divided into three groups (6 mice in each group): keloid group, keloid+SND1 recombinant protein group, and keloid+SND1 recombinant protein+DAA group. Keloid tissue growth was observed by HE staining; the expression level of SND1 in keloid tissue was detected by immunohistochemistry staining and Western blotting. Results The third exon of TINCR contains seven potential RNA methylation sites. The relative expression level and methylation level of TINCR elevated obviously in KFs than in HFs (5.43±0.35 vs. 1.00±0.11, P<0.01; 19.73%±1.56% vs. 10.25%±1.13%, P<0.01), and the protein levels of SND1 and METTL3 in KFs were significantly increased (P<0.01), methylated TINCR could bind both SND1 and METTL3. Compared with empty vector group, overexpression of METTL3 stimulated the mRNA and protein expression of METTL3 (mRNA: 6.03±0.55 vs. 1.09±0.09, P<0.01; protein: 4.33±0.35 vs. 0.96±0.08, P<0.01) and increased the methylation level of TINCR (32.89%±2.88%vs. 19.04%±1.72%, P<0.01) and relative expression level (4.65±0.32 vs. 1.00±0.10, P<0.01). Compared with control group,DAA treatment reduced the stability [(8.50±1.13) h vs. (12.90±1.41) h, P<0.001] and the methylation level (7.43%±0.55% vs.18.88%±1.76%, P<0.01) of TINCR, and inhibited the viability and clonogenic ability of KFs (P<0.01). Compared with control group, SND1 recombinant protein treatment increased the stability of TINCR [(23.95±1.25) h vs. (13.10±1.33) h, P<0.01],cell viability and clonogenic ability (P<0.01), but showed no significant effect on TINCR methylation levels (20.15%±1.74% vs.19.04%±1.77%, P>0.05); DAA treatment may abolish the effect of SND1 recombinant protein on TINCR stability [(12.00±1.21) h vs. (23.95±1.44) h, P<0.01], cell viability and clonogenic ability (P<0.01). Compared with the keloid group, a large number of fibroblasts and collagen fibers existed in the dermal layer of keloid+SND1 recombinant protein group. Furthermore, the percentage of positive SND1 cell and the relative expression level of protein in keloid tissue increased significantly (63.43%±3.32% vs.21.16%±4.67%, P<0.01; 2.54±0.13 vs. 1.00±0.10, P<0.01); However, DAA treatment made large amount of loose fibrous collagen in keloid tissue, and the percentage of positive SND1 cells and the relative expression level of protein decreased significantly(38.52%±6.88% vs. 63.43%±3.32%, P<0.01; 1.07±0.09 vs. 2.54±0.13, P<0.01). Conclusion TINCR is hypermethylated in KFs. SND1 can recognize and bind the methylation sites of TINCR, accelerate the stability of TINCR and promote the growth of TINCR mediated keloid.