〔Abstract〕 Objective This study examined the influence of c-Myc regulated long noncoding RNA TBL1XR1-5(lnc-TBL1XR1-5) on the progression of oral squamous cell carcinoma(OSCC). Methods Based on the expression of c-Myc, bioinformatics analysis was performed on head and neck squamous cell carcinoma samples in theTCGA database, and lnc-TBL1XR1-5 with closely related c-Myc expression was screened.The effects of c-Myc overexpression and knockdown on lnc-TBL1XR1-5 were detected. Expression relationship of c-Myc and lnc-TBL1XR1-5 in OSCC and para-cancer tissues. Dual-luciferase reporter assays were used to verify the binding of c-Myc to the lnc-TBL1XR1-5 promoter region. RNA FISH were used to determine the localization of lnc-TBL1XR1-5 in OSCC cell lines. The effects of overexpression, knockdown of lnc-TBL1XR1-5 on migration, metabolism, and proliferation of OSCC cells were observed by quantitative real-time polymerase chain reaction(qRT-PCR), scratch tests, transwell assays, medium color and pH changes, cell counts, CCK-8 assay, and colony formation assays. Results It was found that c-Myc positively regulated the expression of lnc-TBL1XR1-5 in OSCC cell lines and tissues. The binding of c-Myc to the lnc-TBL1XR1-5 promoter region was verified by dual-luciferase reporter assays. RNA FISH showed that lnc-TBL1XR1-5 was localized in the nuclei in OSCC cells. Overexpression of lnc-TBL1XR1-5 promoted migration, metabolism and proliferation in OSCC cell lines, while knockdown of it had the opposite effect. Conclusion c-Myc positively regulates lnc-TBL1XR1-5 in OSCC. Lnc-TBL1XR1-5 affect the migration, proliferation, and metabolism of OSCC by influencing the tumor microenvironment.