Abstract Background: Oncogenic role of lncRNA LOXL1-AS has been characterized in several types of cancer. Our preliminary deep sequencing data revealed the downregulation of LOXL1-AS in periodontitis and its inverse correlation with IL-1β, a critical inflammatory mediator in periodontitis. This study was therefore performed to investigate the potential interaction between LOXL1-AS and IL-1β in periodontitis.Methods: Research subjects of this study included 30 periodontitis patients and 30 healthy controls. Cell transfection, RT-qPCR, luciferase activity assay and western blots were performed in this study.Results: LOXL1-AS was downregulated in periodontitis-affected periodontal ligament stem cells (PDLSCs) than that in healthy PDLSCs. While IL-1β was upregulated in periodontitis-affected PDLSCs and was inversely correlated with LOXL1-AS. Overexpression of LOXL1-AS mediated the downregulation of IL-1β in PDLSCs. IL-1β treatment did not affect the expression of LOXL1-AS. Moreover, overexpression of LOXL1-AS led to inhibited proliferation of periodontitis-affected PDLSCs. Conclusion: This study is the first to report the downregulation of LOXL1-AS in periodontitis. Moreover, we also propose that LOXL1-AS may inhibit the proliferation of periodontitis-affected PDLSCs and downregulate IL-1β to improve periodontitis.