Patients with oral squamous cell carcinoma (OSCC) have a poor prognosis. The molecular mechanism of OSCC progression remains unclear. The aim of this study was to explore specific prognostic biomarkers of OSCC at the transcriptome-wide level. A total of 158 differentially expressed long non-coding RNAs (lncRNAs), including 85 cis-acting and 10 trans-acting differentially expressed lncRNAs, were screened in OSCC tissues compared with adjacent normal tissues. Both cis- and trans-target genes of differentially expressed lncRNAs were enriched in pathways associated with cancer progression. Additionally, 25 differentially expressed mRNAs were screened. Overlapping analysis of differential protein-coding genes with the cis- and trans-target genes of differentially expressed lncRNAs indicated that KIF19 was the only trans-acting gene of differentially expressed 1ncRNA 'ENST00000626052' (named ENSTa). ENSTa was down-regulated in OSCC tissues and cells, and its low expression corresponded to a poor prognosis in OSCC. KIF19 was highly expressed in OSCC tissues and cells. Patients with high expression of KIF19 had a poor prognosis. Cellular experiments showed that KIF19 expression and cell proliferation were inhibited in cells overexpressing ENSTa. However, KIF19 overexpression counteracted the effect of ENSTa overexpression on cell proliferation. In conclusion, ENSTa regulated the trans-acting KIF19 gene in the inhibition of the progression of OSCC, thus they could be suggested as novel biomarkers for OSCC.