Growing evidence shows that long non-coding RNAs (lncRNAs), such as lncRNA HOXA-AS2, have emerged as critical regulators in human cancer. However, the biological function and detail regulating mechanisms that how lncRNA HOXA-AS2 played in oral squamous cell carcinoma (OSCC) remains unexplored. In this study, high expression of lncRNA HOXA-AS2 was determined in OSCC cell lines and clinical tissues, which positively correlated with advanced TNM stage and poor survival of OSCC patients. In mechanism, we found that lncRNA HOXA-AS2 negatively regulated miR-567 expression by direct interaction. Additionally, we also found that the expression of miR-567 inversely decreased in OSCC tissues along with the up-regulation of lncRNA HOXA-AS2. Functionally, overexpression of lncRNA HOXA-AS2 significantly promoted OSCC cell proliferation, while knockdown of lncRNA HOXA-AS2 significantly inhibited it. Additionally, we determined that miR-567 targeted to CDK8 directly at the 3’ UTR. In conclusion, lncRNA HOXA-AS2 was up-rugulated in OSCC, correlated with poor clinical outcomes, and promoted OSCC cell proliferation via sponging miR-567 to promote CDK8 expression. Therefore, the potential prognostic value of lncRNA HOXA-AS2 could be explored further.