Oral squamous cell carcinoma (OSCC) is a major cancer type in the head and neck region. Recent studies have reported a marked rise in the incidence of OSCC. The present study was performed to better understand the roles that long non‑coding RNAs (lncRNAs) serve in OSCC carcinogenesis. The levels of the lncRNA C5orf66 antisense RNA 1 (C5orf66‑AS1) and of cytochrome c1 (CYC1) in OSCC tissues and cells were measured through reverse transcription‑quantitative polymerase chain reaction. In addition, the levels of associated proteins were analyzed by western blotting, while MTT assay was used to detect the cell proliferation ability. Wound healing and transwell assays were also used to detect the migration and invasion abilities of OSCC cells in the experimental groups, while flow cytometry was applied to analyze cell apoptosis. The findings revealed that the expression of lncRNA C5orf66‑AS1 in OSCC tissues and cells was significantly decreased. Overexpression of lncRNA C5orf66‑AS1 significantly inhibited the proliferation, invasion and migration ability of OSCC cells, and promoted cell apoptosis, while lncRNA C5orf66‑AS1 downregulation presented the opposite effects. In addition, it was observed that CYC1 was upregulated in OSCC tissues and cells, and was negatively regulated by lncRNA C5orf66‑AS1. Notably, CYC1 silencing markedly eliminated the effects of lncRNA C5orf66‑AS1 downregulation on OSCC cells. Taken together, these findings indicated that lncRNA C5orf66‑AS1 may prevent OSCC progression by inhibiting OSCC cell growth and metastasis via the regulation of CYC1 expression.