Objective：To explore the expression and function of long non-coding RNA（lncRNA） CASC9 in oral squamous cell carci－noma（OSCC），and to elucidate its potential mechanisms. Methods：The expression of CASC9 in OSCC tissues from 101 patients was determined by in situ hybridization assay，and the correlation between the expression of CASC9 and clinicopathological characteristics and survival were analyzed. CASC9 siRNA was transfected into the target OSCC cell line SCC15. The mRNA and protein expression levels of PI3K，AKT，and p-AKT in SCC15 cells were measured using qPCR and Western blot，and the proliferation，migration，and invasion of SCC15 cells were evaluated by CCK8 assay，flow cytometry，and Transwell assay，respectively. Results：The expression of CASC9 was significantly increased in OSCC tissues（P=0.000），and it was significantly positively correlated with tumor size，cervical lymph node metastasis，and clinical stage（P<0.05）. The overall survival was significantly shortened in OSCC patients with high expres－sion of CASC9（P=0.007）. CASC9 was an independent risk factor for OSCC（P<0.05）. After silencing of CASC9，the expression of PI3K and p-AKT was significantly reduced（P<0.05），and the proliferation，migration，and invasion of SCC15 cells were significantly attenuated（P<0.05）. Conclusion：CASC9 promotes OSCC progression by activating the PI3K/AKT pathway. CASC9 could potentially be a novel clinical prognostic marker and therapeutic target for OSCC.