Jiandong Li, Xiaohu Xu, Dandan Zhang, Han Lv, Xin Lei Department of Stomatology, Shenzhen Longhua District Central Hospital, Shenzhen, 518000, People’s Republic of ChinaCorrespondence: Jiandong LiDepartment of Stomatology, Shenzhen Longhua District Central Hospital, Shenzhen, 518000, People’s Republic of ChinaEmail lijiandong00111@163.comBackground: Oral squamous cell carcinoma (OSCC) is a common oral cancer. The current study aims to elucidate the potential roles of long noncoding RNA (lncRNA) LHFPL3-AS1 in OSCC development.Methods: Gene expression was measured by qRT-PCR in tumor tissues and cell lines. Loss-of-function assays were performed to analyze the effects of LHFPL3-AS1 on malignant behaviors. Bioinformatics analysis was conducted to explore the downstream signaling pathway of LHFPL3-AS1 in OSCC.Results: LHFPL3-AS1 was highly expressed in OSCC tissues and cell lines. LHFPL3-AS1 was upregulated in cisplatin-resistant tumor cell lines. LHFPL3-AS1 level was correlated with survival rate. LHFPL3-AS1 knockdown suppressed OSCC proliferation, migration and invasion. LHFPL3-AS1 downregulation reduced cisplatin resistance of OSCC cells. LHFPL3-AS1 was the competing endogenous RNA (ceRNA) for miR-194-5p to enhance CHSY1 expression.Conclusion: LHFPL3-AS1/miR-362-5p/CHSY1 signaling pathway plays essential roles in regulating OSCC development and cisplatin resistance.Keywords: oral squamous cell carcinoma, LHFPL3-AS1, miR-362-5p, CHSY1