The study aims to investigate how DANCR can alter the growth and metastasis of oral squamous cell carcinoma (OSCC) cells by regulating miR-216a-5p. The expression of DANCR and miR-216a-5p in OSCC patients and cells were measured. SCC15 and CAL-27 cells were selected to divide into Control, sh-NC, DANCR shRNA, DANCR, miR-216a-5p mimic, and DANCR + miR-216a-5p mimic groups. Dual-luciferase reporter gene assay was performed for the verification of the targeting relationship between miR-216a-5p and DANCR/Bcl-2/KLF12. We also quantified the abilities of OSCC cells regarding proliferation, invasion, migration and apoptosis, and the expression levels of apoptosis-related proteins were measured. Finally, the tumor-bearing nude mice were established to verify the effect of DANCR in vivo. Up-regulated DANCR expression and down-regulated miR-216a-5p expression were observed in both OSCC tissues and cells, and they were proven strongly correlated to the histological grade, clinical staging and lymph node metastasis of OSCC patients. Dual-luciferase reporter gene assay showed a target relationship between DANCR and miR-216a-5p, as well as between miR-216a-5p and Bcl-2/KLF12. Both DANCR shRNA and miR-216a-5p mimic decreased proliferative, migration and invasive abilities of OSCC cells with increased cell apoptosis. However, DANCR group showed completely opposite trends. Moreover, miR-216a-5p mimic could reverse the role of DANCR in promoting tumor growth. In-vivo experiment confirmed the inhibitory role of DANCR shRNA in tumor growth and metastasis. We concluded that DANCR may promote the growth and metastasis of OSCC cells and suppress OSCC cell apoptosis by sponging miR-216a-5p.