Background: IncRNAs perform complex functions and play an essential role in all stages of tumor progression. However, there are few studies that discuss the function of IncRNA ZNF667-ASlin oral squamous cell carcinoma (OSCC). This study aimed at analyzing the expression and biological behavior of IncRNA ZNF667-AS1 in OSCC. Methods: IncRNA ZNF667-AS1 expression level in OSCC tissues and cell lines was explored by real-time PCR The role of IncRNA ZNF667-AS1 on prognosis was elucidated. Cell proliferation assay, plate colony formation assay, wound-healing assay, and transwell migration assay were used to detect cell proliferation ability, cell clone formation ability, migration ability, and invasion ability, respectively. The effect of IncRNA ZNF667-AS1 on epithelial mesenchymal transformation (EMT) process was evaluated by western blot and real-time PCR. Results: The expression levels of IncRNA ZNF667-AS1 were decreased in malignant tumor tissues. The OSCC patients with high expression of IncRNA ZNF667-AS1 had a longer survival time. IncRNA ZNF667-AS1 inhibited cell proliferation, cell clone formation ability, invasion and migration. Furthermore, IncRNA ZNF667-AS1 could inhibit the EMT process by suppressing transforming growth factor-beta-1 (TGF-beta 1) expression, and TGF-beta 1 treatment could partially restore the inhibitory effect. Conclusions: IncRNA ZNF667-AS1 may act as an antioncogene inhibiting the ability of proliferation, cell clone formation, invasion and migration, and suppress the process of EMT by targeting TGF-beta 1. IncRNA ZNF667-AS1 could be a potential therapeutic target and a new predictive biological marker of OSCC.