The role of long non-coding ribonucleic acids (lncRNAs) during orthodontic tooth movement remains unclear. We explored the lncRNA landscape of periodontal ligament stem cells (PDLSCs) subjected to compressive force. PDLSCs were subjected to static compressive stress (2 g/cm2) for 12 hours. Total RNA was then extracted and sequenced to measure changes in lncRNA and messenger RNA (mRNA) expression levels. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expression levels of certain lncRNAs. Differential expression analysis as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also performed. In total, 90 lncRNAs and 519 mRNAs were differentially expressed in PDLSCs under compressive stress. Of the lncRNAs, 72 were upregulated and 18 downregulated. The levels of eight lncRNAs of interest (FER1L4, HIF1A-AS2, MIAT, NEAT1, ADAMTS9-AS2, LUCAT1, MIR31HG, and DHFRP1) were measured via qRT-PCR, and the results were found to be consistent with those of RNA sequencing. GO and KEGG pathway analyses showed that a wide range of biological functions were expressed during compressive loading; most differentially expressed genes were involved in extracellular matrix organization, collagen fibril organization, and the cellular response to hypoxia. The lncRNA expression profile was significantly altered in PDLSCs subjected to compressive stress. These findings expand our understanding of molecular regulation in the mechanoresponse of PDLSCs. © The Author(s) 2018. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.