〔Abstract〕 Objective To explore the action mechanism of long non-coding RNA(lncRNAs) lncRNA KCTD13-DT in oral squamous cell carcinoma(OSCC) and its potential interaction with transcription factor c-Myc, providing a potential diagnostic and therapeutic target for patients with OSCC. Methods The expression of lncRNA KCTD13-DT in OSCC and paracancerous tissues was detected by qRT-PCR. The effects of c-Myc overexpression and knockdown on human tongue squamous carcinoma cells HN6 and CAL27 were detected by qRT-PCR. Fluorescence in situ hybridization(FISH) assessed the localization of lncRNA KCTD13-DT in cells. A dual luciferase reporter gene was used to analyze the role of c-Myc in target binding to the promoter region of lncRNA KCTD13-DT. Stable cell lines with knockdown or overexpression of lncRNA KCTD13-DT were constructed in human OSCC cell lines HN6 and CAL27 by lentiviral infection, and the knockdown and overexpression efficiencies of lncRNA KCTD13-DT were detected by qRT-PCR. Cell proliferation changes were detected by growth curve assay, CCK-8 assay, colony formation assay, and cell migration was detected by scratch assay and Transwell. Results lncRNA KCTD13-DT expression level was reduced in OSCC tissues and OSCC cells(HN6, CAL27), and Western blot verified that after knocking down and overexpression of c-Myc in HN6 and CAL27, the qRT-PCR experiments showed that c-Myc negatively regulated lncRNA KCTD13-DT, and overexpression of c-Myc significantly down-regulated lncRNA KCTD13-DT; knockdown of c-Myc significantly up-regulated lncRNA KCTD13-DT levels. Dual luciferase reporter gene showed that c-Myc could target lncRNA KCTD13-DT, and c-Myc could be involved in regulating and repressing the transcriptional activity of lncRNA KCTD13-DT. FISH showed that lncRNA KCTD13-DT mainly existed in the nucleus. Growth curve assay, CCK-8 assay, cell scratch assay, Transwell, and colony formation assay showed that knockdown of lncRNA KCTD13-DT promoted the growth and proliferation of OSCC cells, and overexpression of lncRNA KCTD13-DT significantly inhibited the proliferation and migration of OSCC cells. Conclusion lncRNA KCTD13-DT is negatively regulated by c-Myc.Knockdown of lncRNA KCTD13-DT promotes cell proliferation, while overexpression of it inhibits cell growth.